THE  LIBRARY 

OF 

THE  UNIVERSITY 

OF  CALIFORNIA 

LOS  ANGELES 

GIFT 

DR.   EMIL  BOGEN 


Vh 


The 

Ransohoff  Memorial  Volume 


A  Collection  of  Papers  Representing  Original 

Contributions  to   the  Art  and  Science 

of  Medicine  by  Colleagues 

and  Students  of 


DR.  JOSEPH  RANSOHOFF, 

M.D..  F.R.C.S.  (Eng.l.  F.A.C.S..  LL.D. 


WB 
^/73 


Nna  #alutamua  Hoh  Sprfnliaaimp  iMnrtuna 

AETERLINCK,  in  one  of  his  most  inspired  plays,  has  originated  a 
very  beautiful  conception  of  the  hereafter.  He  believes  that  far 
away  in  the  Realms  of  the  Infinite,  a  man's  spirit  lives  again  each 
time  that  his  name  is  recalled  or  spoken  here  below.  Man's 
immortality  rests  upon  the  memories  of  him  that  linger  m  the 
thoughts  of  men. 

If  there  be  truth  in  this  answer  to  the  greatest  of  all  questions,  then 
the  spirit  of  the  man  in  whose  honor  this  book  has  been  written,  will  live 
on  in  the  golden  sunlight  of  the  great  love  that  he  left  in  the  hearts  of  his 
fellow-men.  There  was  about  him  a  singular  magnetism,  a  quality  of 
lovableness  that  was  irresistible.  Men  talked  to  him,  told  him  their 
thoughts  and  he  listened,  and  when  they  left  him,  although  he  had  made 
no  effort,  they  felt  they  had  won  a  new  and  very  valuable  friendship.  He 
had  a  deep,  warm  love  for  humanity,  and  each  man's  life  and  each  man's 
happiness  was  worth  his  own  personal   effort   to  guard   against  harm. 

Though  for  over  four  decades  he  practiced  surgery,  he  never  became 
callous  to  the  sight  of  human  suffering.  He  believed  that  the  highest  duty 
of  the  doctor  was  to  alleviate  pain.  With  countless  hundreds  he  walked 
through  the  Valley  of  the  Shadow  of  Death  and  when  he  emerged  with 
them  into  the  glory  of  the  sunshine  once  more,  he  had  their  lasting  confi- 
dence and  friendship.  He  will  live  in  the  thoughts  of  these  people  as  he 
was  to  them  in  their  hour  of  trial,  the  healer  and  the  friend. 

He  loved  youth  and  the  wholesome  out-of-door  pleasures  of  youth. 
His  happiest  summers  were  passed  with  a  band  of  young  men  in  the 
Canadian  woods,  where  he  tramped  and  fished  and  smoked  and  read  and 
cooked  marvelous  hsh  chowders  for  an  enthusiastic  group  of  hungry  young- 
sters. To  watch  him  hook  and  play  and  land  a  huge  "musky  "  with  those 
delicate  surgeon's  hands  of  his  was  a  treat  for  a  true  sportsman.  And 
because  he  knew  and  loved  and  understood  the  ways  of  youth  he  was  able 
to  impart  to  young  men  the  difficult  art  of  his  beloved  profession  as  few- 
have  been  able  to  teach  it.  His  bedside  clinics  were  invested  with  a  flash 
of  genius.  His  teachings  meant  more  to  his  pupils  than  the  dry  accumula- 
tion of  facts  necessary  to  pass  examinations  and  make  a  livelihood.  They 
meant  the  handing  on  of  a  sacred  trust  from  the  old  generations  to  the 
new.  So  he  will  live  in  the  hearts  of  the  men  he  taught,  revered  by  them 
as  the  great  teacher  who  loved  and  understood  them. 

In  the  store-house  of  his  mind  lingered  fragments  and  bits  of  prayers 
from  the  old,  old  faith  of  his  forefathers.  Many  an  old  patriarch  with 
sorrow-clouded  eyes,  lying  lonely  and  suffering  in  the  wards,  would  brighten 
into  happiness  when  this  man,  in  passing  his  bed,  would  stop  to  wish  him 
well  or  whisper  a  time-worn  phrase  in  the  dialect  of  his  own  people. 

He  loved  the  beautiful  things  of  life,  books,  music,  nature.  But,  above 
all  else,  he  loved  with  a  fierce  intensity  the  work  to  which  he  devoted  the 
years  and  strength  of  his  manhood.  Before  he  died,  he,  who  had  given  the 
world  so  much,  said:  "I  have  had  a  perfect  life;  the  world  owes  me 
nothing.  " 

When  he  died  the  highest  and  the  most  obscure  sent  messages  telling 
of  the  loss  they  had  sustained  in  his  passing. 

He  had  a  great  mind  and  a  gentle  soul.  The  world  is  richer  for  his 
having  lived. 


(Eantents 

PAGE 

Nos  Salutamus  Vos  Recentissime  Mortiios iii 

Editor's    Preface vii 

Dr.  Joseph  Ransohoff 1 

Publications  of  Dr.  Joseph   Ransohoff 7 

Elmer  R.  Arn  : 

The  Therapeutic  Possibilities  of  Blood  Transfusion — Methods,  Indications 
and   Results 13 

Albert  J.  Bell  : 

Observations  Upon  Scarlet  Fever,  Diphtheria  and   Measles  at  the  Cincinnati 

Contagious  Hospital 23 

Julien  E.  Benjamin  and  Sidney  Lange  : 

Report  of  Nineteen  Cases  of  Hyperplasia  of  the  Thymus  Gland   Treated  by 

the  X-Rays 36 

Oscar  Berghausen  and  Chas.  E.  Howard  : 

The  Treatment  of  Wounds,  vi'ith  Reference  to  Tetanus  Prophylaxis 42 

Kenneth  D.  Blackfan  : 

The  Early  Recognition  of  Hydroceplialus  in  Aleningitis 4C> 

George  Emerson  Brewer  : 

Standards  of  Success  in  Medicine 5(5 

Mark  A.  Brown  : 

Multiple  Infections 64 

Robert  B.  Cofield  : 

Disinfection  of  the  Knee  Joint 71 

George  W.  Crile  : 

The  Mechanism  of  Shock  and  Exhaustion 75 

Joseph  L.  DeCourcy  : 

Thyroidectony— A  Brief  Review  of  137  Cases 91 

Albert  Faller: 

Sources  of  Wassermann  Error  and  Their  Control 96 

Leonard  Freeman  : 

Primitive  Surgery  of  the  Western  Hemisphere 101 

Albert  H.  Freiberg  : 

Wolff's  Law  and  the  Functional  Pathogenesis  of  Deformity 114 

Alfred  Friedlander  and  Carey  P.  McCord  : 

The  Atropin  Test  in  the  Diagnosis  of  Typhoid  Infections 129 

Alfred  Friedlander  and  J.  Victor  Greenep.aum  : 

Note  on  the  Influence'of  Food  Upon  the  Intestinal  Flora  of  Infants 136 

W.  D.  Haines  : 

Tumors  of  the  Mediastinum 144 

William  S.  Halsted  : 

A  Striking  Elevation  of  the  Temperature  of  the  Hand  and  Forearm  Following 
the  Excision  of  a  Subclavian  Aneurism  and  Ligations  of  the  Left 
Subclavian  and  Axillary  Arteries 150 

Meyer  L.  Heidingsfeld  : 

The  Pathology  of  Chromidrosis 161 

Harry  H.  Hines  : 

Brain   Decompression   Operations 171 

Christian  R.  Holmes: 

Hospitals — History  of  Their  Development 175 

Herman  H.  Hoppe: 

i.     The  Medical  Treatment  of  Graves'  Disease  with  Special  Reference  to  the 

Use  of  Corpus  Luteuin  Extract 186 

ii.    The  Treatment  of  Hyperthyroidism  with  Corpus  Luteum 193 


CONTENTS— Continued. 

PAGE 

Samuel  Ici.auer: 

i.     The  X-Ray  Examination  of  tlic  Mastoid  Region 202 

ii.    The  Clinical  Value  of  Radiography  of  the  Mastoid  Region 211 

Raphael  Isaacs  : 

The  Structure  and  Mechanics  of  Developing  Connective  Tissue 217 

Dennis  E.  Jackson  and  Gerard  Raap  : 

An  Experimental  Investigation  of   Certain   Features   of   the   Pliarmacological 
Action   of    Salvarsan 237 

Howard  A.  Kelly  : 

A  Case  of  Cancer  of  the  Vagina,  Cervix  and  Body  of  the  Uterus,  Treated 

by    Radium 254 

Thomas  H.  Kelly  and  Hiram  B.  Weiss  : 

The  Diagnosis  and  Treatment  of  Diaphragmatic  Pleurisy 258 

Henry  McE.  Knower  : 

Demonstration  of  the  Interventricular  Muscle  Bands  of  the  Adult  Human  Heart  3G7 
George  H.  Kress  : 

Ocular  Angio-sclerosis 268 

Frank  W.  Langdon  : 

Biologic  Aspects  of  Dementia  Praecox 275 

Louis  A.  Lurie  : 

Pernicious  Anaemia  with  Mental  Symptoms 286 

Benj.  F.  Lyle  : 

The  Tuberculosis  Problem  in  Cincinnati 322 

Merrick  F.  McCarthy  : 

Dizziness 316 

Carey  Pratt  McCord  : 

The  Pineal  Gland 355 

Edward  F.  Malone  : 

The  Nucleus  Cardiacus  Nervi  Vagi  and  the  Three  Distinct  Types  of   Nerve 

Cells  which  Innervate  the  Three  Different  Types  of  Muscle' 308 

Edward  C.  Mason  and  Carl  E.  Pieck  : 

A  Pharmacological  Study  of  Benzyl  Benzoate 374 

William  J.  Mayo  : 

Relation   of   the   Development   of   the   Gastro-Intestinal    Tract    to    Abdominal 

Surgery  391 

Willy  Meyer  : 

The  Necessity   for  the  Application   of   Differential   Air-Pressure   in   Thoracic 
Operations    402 

Roger  S.  Morris  : 

Blood  Formation  in  the  Liver  and  Spleen  in  Experimental  Anaemia 412 

A.  J.  Ochsner  and  D.  W.  Crile: 

Clinical  Consideration  of  Osteomyelitis 420 

Wade  W.  Oliver  : 

A  Rapid  Method  of  Pneumococcus  Typing 445 

Dudley  W.  Palmer  : 

Hyperplastic  Pyloric  Stenosis  of  Infancy 449 

J.  Edward  Pirirung  : 

Complications  and  End  Results  of  Bile  Duct  Infection 455 

Benjamin  Knox  Rachford  : 

The  Influence  of  Bile  on  the  Fat-Splitting  Properties  of  Pancreatic  Juice 401 

J.  Louis  Ransohoff: 

Adherent  Hernias  of  the  Large  Intestine 480 

William  Ravine: 

The  Dangers  and  Fallacies  of  Intraspinous  Injection  of  Salvarsan 493 


CONTENTS— Continued. 

PACE 

Augustus  Ravogli  : 

On  the  Strictures  of  the  Male  Urethra 501 

Moses  Salzer  : 

A  Case  of  Tin  Poisoning 511 

M.  G.  Seelig  : 

Rhinophyma  514 

E.  Otis  Smith  : 

Anatomy  and  Pathology  of  the  Seminal  Vesicles 520 

Chas.  T.  Souther: 

Inguinal   Hernia    528 

Robert  W.  Stewart  : 

Toxicity  of  Urine  in  Pregnancy 540 

Elmore  B.  Tauber: 

The  Early  Diagnosis  of  Syphilis :  .   549 

William  B.  Wherrv  and  C.  T.  Butterfield  : 

Inhalation  Experiments  on  Influenza  and  Pneumonia,  and  on  the  Importance  of 

Spray-Borne  Bacteria  in  Respiratory  Infections .555 

Hiram  B.  Weiss: 

The  Principles  and  Treatment  in  Mercuric  Chloride  Poisoning 504 

Philip  Zenner  : 

The   Venereal   Problem 509 


iEJiitnra'   Prrfarr 

N    an    effort    to    express    to    Dr.    Joseph    Ransohoff    their 

appreciation    of    his    place    m    the    science    and    art    of 

Medicine  a  group  of  his  former  students  determined  to 

issue   a  volume   containing   papers   consisting   of   original 

contributions    to    the    advancement    of    Medicine    by    his 

students  and  colleagues.     This  was  in  June,  1920.     The 

death     of    Dr.    Ransohoff    prevented    the     presentation     of     this 

book  to  him  personally,  but  the  publication  was  continued   as   a 

Memorial   Volume. 

The  Editors  wish  to  express  their  appreciation  to  the  many 
friends  of  Dr.  Ransohoff  for  the  help  they  have  given  in  making 
this  work  a  reality,  and  to  the  S.  Rosenthal  &  Co.  for  their  part 
in  the  printing  of  this  book.  Recognition  is  given  to  the  publishers 
of  the  different  articles  for  permission  to  reprint  them  in  this  book. 

EDITORIAL  BOARD 

Dr.    A.   C.   Bachmeyer  Dr.   J.    C.   Oliver 

Dr.   Julien   Benjamin  Dr.    B.    K.    Rachford 

Dr.   Nora   Crotty  Dr.   Samuel   Rothenberg 

Dr.   Martin  H.   Fischer  Dr.   Robert  Sattler 

Dr.   Frederick   C.   Hicks  Dr.    E.  O.  Smith 

Dr.    Carl   HiUer  Dr.    Robert   Stewart 

Dr.    Raphael    Isaacs  Dr.    Wm.    B.    Wherry 
Dr.   Albert   Mathews 


®fl  ir.  3lnBrpI|  SatiHnlinff 

Anatomist,  .burgeon,  v^chnlar,  iM-itiul  and  'readier;  to  you  is  dedicated 
this  book.  Ikil  abo\e  all  to  ycui  as  teaclier.  P'niinent  in  all  of  your  under- 
takings, as  teacher  have  you  been  pre-eminent,  and  the  men  who  throughou' 
forty-two  years  have  known  you  thus,  inscribe  to  you  this  tribute  of  af- 
fection and  of  homage. 

Friend  and  Teacher:  the  hope  had  been  cherished  to  i)resent  to  \ou  this 
enduring  token,  while  your  eye  was  still  undimmed  a)id  your  tongue  stil! 
able  to  serve  in  its  way,  inimitable.  Within  a  few  short  months  Fate  ha,- 
taken  from  us  this  great  privilege.  To  the  wreath  of  immortality  whicli 
you  have  woven  for  yourself  m.ny  we  be  permitted  to  add  a  few  leaves. 
"Memory  is  a  net;  one  finds  it  full  df  tish  when  he  takes  it  from  the  brook; 
but  a  dozen  miles  of  water  ha\c  run  through  it  without  sticking."  There- 
fore, let  us,  your  friends  and  jjupils,  wander  gently  through  the  years  which 
you  have  s])ent,  that  for  us  and  those  who  come  after  us  they  may  have  an 
imperishable  record. 


For  sixty  years  has  stood  the  church  of  the  Franciscan  Fathers  in  Cin- 
cinnati. For  sixty  years  has  the  grimy  figure  of  St.  Francis  of  Assisi 
looked  down  upon  Liberty  street ;  venerated  by  many  devout  passersby,  but 
also  the  butt  of  many  a  jest  from  the  mischievous  boys,  who,  throughout 
many  years,  found  in  the  narrow  street  below  their  only  playground.  To 
the  east  a  garden,  closed  in  by  a  high  brick  wall,  separates  the  church  from 
Vine  street ;  even  now,  after  the  passing  of  two  generations  of  men,  a  fairly 
busy  thoroughfare,  it  was  formerly  very  dififerent  in  its  aspect.  Abounding 
in  many  small  shops,  the  street  is,  in  the  daylight  hours,  perhaps  not  greatly 
changed  in  appearance.  The  dethronement  of  King  Gambrinus  has,  how- 
ever, played  havoc  with  its  nocturnal  glory.  Here  we  are  almost  at  the 
northern  terminus  of  that  region  for  so  many  years  gaily  spoken  of  a; 
"Over  the  Rhine."  And  it  was  so  spoken  of  not  merely  in  gayety,  but  also 
most  aptly ;  in  its  houses  and  in  those  of  the  contiguous  streets  lived  a 
populace  prevailingly  German.  Few,  indeed,  were  the  persons  one  might 
have  encountered  here  sixty  years  ago  who  would  have  failed  to  compre- 
hend a  (German  salutation,  and  fewer  still.  Ibosr  wli,,  would  have  failed  lo 
resiiond  to  it  politely  and  respectfully.     In  place  of  the  brilliant  electric  il- 


RAXSOHOFF  MFMOR/.iL  VOLUME 


lumination  of  our  time,  emphasized  by  the  gaudy  resplendence  of  the 
"movies"  found  in  every  block,  we  would  have  found  only  flickering  gas 
lamps.  The  many  "Bierstuben"  with  which  the  street  abounded  were,  for 
the  most  part,  lighted  with  oil  lamps,  and  the  evening  found  their  tables 
bearing  many  glasses  of  foaming  "Lager,"  behind  which  sat  decent,  thrifty 
and  sober  men  who  had  wandered  from  the  "Fatherland"  long  before 
it  went  mad  with  war  lust.  Some  of  them,  indeed,  were  forty-eighters.  who 
sought  this  country  in  search  of  liberty  and  opportunity,  and  found  both. 
If  our  imaginations  carry  us  into  these  rooms  with  ears  as  well  as  eyes, 
we  shall  hear  serious  talk ;  in  this  year  of  1860  was  Abraham  Lincoln  ele- 
vated to  his  troublous  eminence  and  the  premonitions  of  the  Civil  War  were 
in  the  minds  and  the  mouths  of  men.  Then,  from  the  houses  of  German 
\'ine  street  and  the  many  habitations  of  the  neighborhood  went  forth  hun- 
dreds of  these  "German  citizens"  and  their  sons  to  prove  with  their  blood 
and  their  lives  how  real  was  their  allegiance  to  the  Union;  just  as  the  sons 
and  the  grandsons  of  these  same  men  have  not  hesitated  to  show  it  again  in 
our  day  in  a  manner  more  telling.  For  now  the  enemy  had  become  the  same 
"Fatherland"  whence  their  forebears  had  been  derived. 

The  church  of  St.  Francis  is  not  a  beautiful  edifice;  quite  the  contrary. 
From  a  facade  severely  plain  there  rise  two  spires,  as  were  there  two 
routes  to  the  empyrean;  for  if  the  unmoving  hands  of  the  clock  in  the  on?^ 
are  at  a  quarter  before  five,  those  of  the  other  say  that  it  is  half  past  eleven. 
The  western  windows  of  the  church  give  upon  a  narrow  street,  called  ISremen 
street  until  1918.  Then  in  the  spirit  of  belligerent  patriotism  the  name 
was  changed  to  the  present,  Republic  street.  In  an  unpretentious  brick 
house  on  Bremen  street,  just  north  of  St.  Francis  Church,  lived  Xathau 
Ransohoflf,  and  here  was  spent  the  boyhood  and  youth  of  his  only  son  and 
yoimgest  child.  Joseph.  Nathan  Ransohoff  came  to  Cincinnati,  almost  one 
liundred  years  before  these  lines  were  written,  from  Westphalia,  where  in 
his  family  there  had  been  men  of  culture.  If  great  fame  was  not  theirs, 
neither  were  they  without  local  distinction,  and  a  prized  possession  of 
Joseph  Ransohofif's  was  the  portrait  of  his  uncle,  with  a  decoration  upon 
his  breast  in  token  of  his  successful  work  among  the  people  with  whom 
he  lived.  It  is  interesting  that  the  stranger  to  this  city  found  here  friends 
in  the  persons  of  Jacob  and  Sarah  Workum,  natives  of  Amsterdam,  the 
maternal  grandparents  of  Minnie  Workum  Freiberg,  who  many  years  after- 
ward became  Mrs.  Josejih  Ransohoff. 

Folk  of  a  pious  Jewish  orthodoxy  were  Nathan  and  Esther  Ransohoff. 
Content  with  the  modest  mercantile  success  which  had  come  to  them,  they 
were  also  satisfied  to  live  quietly  in  the  shadow  of  St.  Francis  Church,  with 
its  mute  and  unintentional  suggestion  that  there  is  more  than  one  way  to 
that  realm  which,  for  mortals,  is  impenetrable  and  unknowable.  Here 
l)layed  the  boy.  "the  hope  of  the  name."  He  had  been  intended  for  the 
rabbinate  by  his  parents,  and  with  this  in  view  there  was  laid  the  foundation 

Page  2 


DR.  JOSEPH  RANSOHOFF 


for  extended  training  in  Hebrew  lore  and  tradition  which  had  an  effect  upon 
his  mind  and  character,  enduring  to  the  last  and  which  often  occasioned 
surprise  to  those  who  were  themselves  thus  learned.  The  public  school 
of  the  neighborhood  and  Woodward  High  School  gave  him  all  that  he 
received  of  systematic  secular  training.  After  his  graduation  from  high 
school,  in  1870,  he  passed  directly  into  the  study  of  medicine.  The  Medical 
College  of  Ohio,  from  which  he  was  graduated  in  1874,  was  one  of  the  best 
known  medical  schools  of  the  country  of  that  day,  as  well  as  one  of  the 
largest.  Graham,  Blackman,  M.  B.  Wright,  Reamy  and  Bartholow,  these 
were  the  men  who  inspired  the  young  medical  student  with  high  ideals  of 
medical  pedagogy  and  of  scholarship.  Of  these  none  exercised  a  more 
potent  and  lasting  influence  than  Graham,  and  I  have  heard  Ransohoff  say, 
more  than  once,  that  in  all  of  his  student  wanderings  he  had  met  with  nt 
more  brilliant  or  gifted  teacher;  his  style  of  teaching  he  characterized  as 
"histrionic."  In  my  mind's  eye  I  see  the  father  Ransohoff  returning  to  his 
simple  home  from  the  synagogue  on  the  Sabbath  eve  (Friday)  of  February 
27,  1874.  I  see  him  celeljrating  the  Sabbath  meal  in  its  traditional  beauty : 
I  see  the  family  walking  the  long  way  down  \'ine  street  to  Fourth ;  I  see 
them  seated  in  Pike's  Opera  House,  where  the  commencement  exercises 
of  the  Medical  College  of  Ohio  were  held.  But  above  all,  I  see  the  pridj 
in  the  faces  of  mother  and  father  as  they  see  their  son,  the  youngest  of  the 
class,  called  forth  to  receive  the  gold  medal  from  the  hand  of  Thaddeus  A. 
Reamy  for  his  essay  on  Puerperal  Eclampsia.  How  singular,  perhaps  in 
no  branch  of  his  profession  was  he  afterward  destined  to  have  a  less  active 
interest  than  in  obstetrics.  Before  his  graduation  he  had  already  served 
as  intern  in  the  Cincinnati  Hospital ;  he  has  told  me  that  the  degree  of 
M.  D.  was  conferred  only  after  the  year  of  internship  in  order  to  hold  the 
young  men  in  the  hospital.  The  food  was  so  poor  that  defections  before 
the  end  of  the  term  could  not  be  otherwise  prevented. 

After  his  graduation  he  proceeded  to  Germany  for  graduate  study, 
and  it  was  his  father's  wish  that  he  should  obtain  a  European  degree.  Wurz- 
burg,  Berlin,  \ienna,  Paris  and  London,  these  were  the  places  of  abode  and 
earnest  study  until  his  return  to  Cincinnati  in  1877.  Kolliker,  \'irchow 
Langenbeck,  Billroth,  Tillaux,  Paget  and  Jonathan  Hutchinson ;  Hebra, 
Rokitansky  and  Gerhardt,  these  are  the  names  of  men  often  spoken  of  by 
Ransohoff  by  reason  of  the  influence  which  they  had  exerted  upon  his  de- 
velopment, both  as  practitioner  and  as  teacher.  Having  proceeded  to  Lon- 
don, Ransohoff  applied  himself  energetically  to  preparation  for  the  exam- 
ination for  Membership  of  the  Royal  College  of  Surgeons  of  England. 
This  was  the  degree  which  he  hoped  to  bring  back  in  response  to  his  father's 
wish.  The  difficulty  lay  chiefly  in  extremely  rigid  tests  in  anatomy:  the 
Fellowship  degree  seemed  altogether  beyond  jjossibility  in  its  demand  for 
the  utmost  in  the  way  of  anatomical  and  surgical  knowledge.  It  was 
practically  never  taken  until  at  least  one  year  after  the  Membership  had 
been  conferred,  and  it  seemed  time  to  return  to  America  and  to  take  up 


KAXSOnOFF  MEMORIAL  VOLUME 


the  pursuit  of  the  practice  for  which  he  had  been  so  long  and  so  arduously 
preparintj.  The  M.  R.  C.  S.  was  given  him  in  April,  1877.  Some  days 
afterward,  while  working  in  the  wonderful  Hunterian  Museum,  he  was 
recognized  by  Sir  James  Paget ;  he  complimented  him  upon  his  brilliant 
examination  and  urged  him  to  try  for  the  Fellowship.  This  resulted  in  his 
obtaining  the  greatly  coveted  F.  R.  C.  S.  in  June.  1877,  under  conditions 
almo.st,  if  not  altogether,  unprecedented.  Immediately  thereafter  RansohofY 
returned  to  Cincinnati. 

Heralded  by  this  remarkable  accomplishment,  it  was  easy  for  him  t.; 
obtain  recognition  in  the  Medical  College  of  Ohio.  Late  in  the  summer  of 
1877  he  was  made  Demonstrator  of  Anatomy  and  began  to  teach  surgery 
in  the  college  dispensary.  In  1879,  the  untimely  death  of  the  brilliant  Lan- 
don  Longworth  made  a  place  for  him  as  Professor  of  Descriptive  Anatomy. 
Remarkable  didactic  talent  such  as  Ranschoff  possessed  insured  for  him  im- 
mediate advancement  as  the  opportunities  appeared.  He  soon  was  made  a 
member  of  the  staff  of  the  Good  Samaritan  Hospital  and  began  to  hold 
surgical  clinics,  which  were  eagerly  attended  by  the  students,  who  were 
not  long  in  appreciating  his  unusual  ability  as  a  teacher,  even  as  the  new- 
comer to  a  group  made  up  of  men  like  Dawson,  Reamy,  Conner.  \\'hitta- 
ker  and  his.  as  well  as  our,  lamented  friend,  Frederick  Forchheimer.  Since 
1902  Ransohoiif  occupied  the  Chair  of  Surgery  in  the  Medical  College  of 
Ohio  and  in  the  University  of  Cincinnati,  with  the  organization  of  a 
veritable  university  faculty  in  1909.  It  was  his  privilege  to  li^■e  to  see  the 
fulfillment  of  a  prophecy  which  was  made  at  this  time  by  one  who  dis- 
believed in  its  probability,  when  he  wrote : 

'Tf  the  lessons  of  the  recent  past  are  heeded,  if  the  ambition  of  ihe  in- 
dixidual  is  tempered  by  love  of  science  and  by  civic  patriotism,  if  the  uni: 
is  willing  to  be  absorbed  by  the  totality  of  the  purpose  embodied  in  the  whole, 
then  Medical  Cincinnati  may  rise  again  in  all  her  old-time  glory,  an  im- 
perishable monument  to  the  great  Daniel  Drake,  whose  genius  hovers  about 
the  old  town,  where  \\'estern  medicine  was  born  and  grew  into  a  vigorous 
adolescence  and  heroic  manhood." 

With  the  occupation  of  the  new  Cincinnati  General  Hospital  came  the 
opi^ortunity  for  the  full  flowering  of  the  genius  of  Joseph  Ransohofif  as  a 
teacher  of  clinical  surgery,  and  the  climax  was  reached  with  the  installation 
of  the  Medical  College  in  its  jiresent  magnificent  building  on  the  sam-^ 
grounds;  it  was  now  possible  to  do  things  for  the  student  of  medicine  not 
dreamed  of  when  he  began  his  career  as  teacher.  The  opportunity  which 
he  now  had  for  devoting  a  greater  amount  of  time  to  teaching  was  seized 
with  eagerness ;  an  eagerness  which  could  not  have  been  greater  had  it 
been  the  first  chance  of  his  life  to  show  his  ability  and  to  establish  his 
reputation.  It  were  entirely  fruitless  to  attempt  the  analysis  of  his  success 
as  a  teacher.  A  sufficient  explanation  is  found  in  his  enthusiasm  and  in 
that  of  his  students.  That  he  had  passed  the  time  of  life  when  teachers 
of  medicine  commonly  relincinish  a  large  part  of  their  work,  seeking  greater 

Fayc  i 


DR.  JOSEPH  RANSOHOFF 


leisure  and  relief  from  routine  burdens,  was  never  apparent  to  him  in  his 
own  self -consciousness,  I  am  sure.  (3n  the  contrary,  he  shrank  from  the 
thought  that  he  might  live,  being  no  longer  a  teacher  of  surgery. 

Xature  had  been  very  kind  to  Joseph  Ransohoff,  not  only  in  giving 
him  an  active,  clear-thinking  brain  and  a  remarkably  retentive  memory, 
but  with  these  a  pleasing  voice,  a  charm  of  presence  and,  above  all,  a  lov2 
for  what  was  fine  and  beautiful.  The  history  of  his  profession  and  of  the 
outstanding  figures  there  to  be  found  liad  an  irresistible  lure  for  him ;  he 
was  therefore  learned  not  only  in  the  technical  side  of  medicine  and  sur- 
gery, but  also  in  the  story  of  its  development  as  art  and  science.  His  ad- 
dresses in  this  field  were  not  many,  but  they  were,  all  of  them,  notable  an.J 
characterized  by  grace  of  diction  and  charm  in  the  manner  of  their  deliver}'. 
That  he  had  both  talent  and  love  for  literary  effort  not  at  all  connected 
with  his  profession  is  not  as  well  known  as  it  should  be.  He  wrote  a  num- 
ber of  stories  of  distinct  merit,  but  they  were  not  published.  Surely  the 
crowning  effort  of  his  life,  in  its  relation  to  the  Medical  College  and  to  rhe 
public,  was  presented  on  that  delightful  November  day  of  1920,  when  there 
was  celebrated  the  centennial  of  the  medical  school.  Ransohoff's  unbounded 
admiration  for  Daniel  Drake,  the  great  founder,  and  his  personal  love  for 
Christian  R.  Holmes,  the  great  builder,  made  easy  for  him  the  composition 
of  his  address,  "Drake  and  Holmes,"  which  completely  captivated  an  audi- 
ence which  overfilled  the  auditorium  of  the  college  building.  This  was  for 
him  a  great  day,  not  only  in  the  personal  triumph  which  he  achieved,  but 
because  there  was  conferred  upon  him  by  his  Alma  Mater  the  degree  of 
Doctor  of  Lav>-s.  This  was  a  reward,  not  too  great,  for  more  than  fort\- 
years  of  devoted  service  of  high  value  and  conspicuous  results.  Aias !  thai 
it  should  also  have  marked  his  last  appearance  in  that  auditorium. 

It  were  superfluous  to  emphasize  here  in  what  high  degree  Ransohoff 
was  a  remarkable  and  successful  practitioner  of  surgery.  In  addition  t.i 
learning,  manual  dexterity,  remarkable  clinical  judgment  and  even  intuition, 
he  had  a  grace  of  manner  and  a  symjiathy  for  those  who  suffered,  which 
endeared  him  to  his  patients,  exceedingly.  He  came  into  surgery  at  t'lc 
beginning  of  its  most  active  and  fruitful  ]:)eriod.  Change  followed  upon 
change,  innovation  upon  innovation,  but  Joseph  Ransohoff  was  able  to 
pass  from  the  scenes  of  his  labors  after  a  long  career  of  uninterrupted 
activity,  conscious  of  the  fact  that  he  was  always,  and  to  the  end,  abreast 
of  the  times,  marking  with  his  own  feet  the  forefront  of  progress. 

"-\nd  tho',   in  tliis  lean  age   forlorn, 

Too   many   a   voice   may   cry- 
That   man   can   have   no   after-morn, 

Not  yet   of   these   am    I. 
The    man    remains,    and    vvhatso'er 

He  wronght  of  good   or  Ijrave 
Will  mould  him  thro'  the  cycle-year 

That   dawns    behind   the    grave." 


Fratcr,  avc  aUjiic  7'alc. 

ALBERT  H.  FREIBERG. 


^ubliratinna  of  ir.  DflBPjjI^  ?Rananl|off 

1879 
A  Contribution  to  the   St'.idy  of   the   Operation    for   Hare   Lip.      ( Cin.   Lancet-C'l 

1879,  V.  :\  p.  1-3.) 
Tetanus;  Nerve  Stretching;  Cure.     (Cin.  Lancet-Clinic.  1871),  v.  2,  p.  41-4:!.) 


Aneurism   of   the    Innominate   and    .\orta;    Ugature   of   the    Carotid    and    Subclavian 
,\rteries;   Death  on  the  Seventh   Uav.     ( .\ni.  J.  Med.  Sc,  IMSO,  v.  Xn,  p.  ;!."r2-.",il. ) 
Hernia  of  the  .-XbduCor  Lon.yi.:s.     (Cm    Lancet-Clinic,  lst<0,  v.  4,  p.  .jii.) 

1881 

Erysipelatous  Inflammation  of  the  Glottis.     (Cin.  Lancet-Clinic,  1881,  n.  s.  v.  7,  p.  .M:'..) 
Permanent  Perineal  Fistula.     (Cin.  Lancet-Clinic,  1881,  n.  s.  v.  <i,  p.  '■'•'>.) 
Rare  Cases  of  Syphilis.     (Cin.  Lancet-Clinic.  1881,  n.  s.  v.  7,  p.  !-l.) 


A  Contribution  to  the  Sur.«ery  of  the  Liver.     (Med.  Rec.  1882,  v.  22,  p.  2")8-()l.) 
Ein  Beitrag  zur  Chirurgie  der  Leber.     (Berl.  Klin.  Wchnschr.,  1882,  v.  19,  p.  600-003.) 
Fibroid  Polypus  of  the  Rectum.      (Cin.  Lancet-Clinic,  1882,  n.  s.  v.  8,  p.  486.) 
Gunshot  Injury  of  the  Shoulder.     (Ciu-  Lancet-Clinic,  1882,  n.  s.  v.  8,  p.  l-t.) 
Tetanus   from   Injury  by  Toy    Pistol;   Stretching   of   the   Median  and   Ulnar   Nerves; 
Death.     (Cin.  Lancet-Clinic.  18,>^2.  n.  s.  v.  9,  p.  200.) 

1883 

[Discussion.]      (Cin.  Lancet-Clinic,  18.^:!,  n.  s.  v.  lo,  p.  4!):..) 

Early  Trephining  in  Diseases  of  Bones.     (J.  Am.  Med.  Ass.,  1883,  v.  1,  p.  299-302.) 
Epithelioma  of  the  Lips.     (Cin.  Lancet-Clinic,  1883,  n.  s.  v.  10,  p.  447-49.) 
Papilloma  of  the  Bladder;  Operation;  Cure.    (Med.  News,  Phila.,  1883,  v.  42,  p.  1"):1-5C.) 
Retro-Peritoneal  Cysto-Sarcoma.     (Med.  News,  1883,  v.  43,  p.  .j7."i-77.) 
The   Treatment   of   Empyema   by   Pleural    Incision;    Report   of    Three    Cases.      (Cin. 
Lancet-Clinic,  1883,  n.  s.  v.  11,  p.  431-.3.^.) 

1884 

Sanguineous  Cyst  of  the  Neck.     (Cin.  Lancet-Clinic,  1884,  n.  s.  v.  13,  p.  1-4.) 

1885 

Two  Ovariotomies  in  the   Same   Patient.      (Med.   News,   LSS.'i,  v.  47,  p.   11."j-19.     .Also 

reprint.) 
Two  Ovariotomies  Successfully  Performed  on  the  .Same  Patient.     (Cin.  Lancet-Clinic, 

188.J,  n.  s.  V.  14,  p.  :,m-'.n.) 
Urethral  Calculi.     (J.  Am.  Med.  .Ass.,  18)S.-,,  v.  5,  p.  (I.V07.) 
Urethral  Calculi.     (Tr.  Ohio  Med.  Soc,  188.-..  ,>.  1(19-73.) 


.\  Case  of  Aortic  .'\neurism  Treated  by  the  Insertion  of  Wire.     (J.  .\m.  Med.  .\ss., 

1880,  V.  7,  p.  481-8.-).) 
A  Case  of  Aortic  Aneurism  Treated  by  the  Insertion  of  Wire.     (Med.  News,  Phila., 

1886,  V.  48,  p.  .597-602.) 
A  Case  of  Aortic  Aneurism  Treated  bj  the  Insertion  of  Wire.     (Phila.,  1880,  18p.,  12°. 

[Repr.  from   Med.   News,   188().l  ) 
Tracheotomy;  a  Report  of  Nine  Cases.     (Med.  &  Surg.  Reporter,  1880,  v.  'A.  p.  2Cll-(i2.) 
Tracheotomy  in  Diphtheritic  Croup.     (Lancet-Clinic,  1880,  n.  s.  v.  10,  p.  9.-|,  disc,  p.  1(17.) 

Page  7 


RAXSOHOFF  MEMORIAL  VOLUME 


Considerations    on    the    Anatomy,    Physiology,    and    Pathology    of    tlie    Caecnm    and 

Appendix.     (J.  Am.  Med.  Ass.,  lf<88,  v.  11,  p.  40-46.) 
Gastro  Enterostomy;  a  Clinical  Lecture.     (Polyclinic,  1889-90,  v.  li,  p.  -il'll-ll. ) 
Old  Bilateral   Dislocation  of  the  Elbow,  With   Report  of  Two  Cases.     (Cin.   Lancet- 
Clinic,   1889,  n.  s.  y.  I'.l,  p.   IJ-MC;  also  J.   Xat.   Ass.   Railway   Surg..    1889,  v.  •_', 
p.  1-28-34.) 

1890 
Fractura  Basis  Cranii.     (J.  Med.  Coll.,  Ohio,  1890,  v.  1,  p.  29.) 
Valedictory  Address.      (Lancet-Clinic,   Mch.  8,   1890.) 

Rupture    of    Middle    Meningeal    Artery    Without    Fracture;    Ligature    of    Common 
Carotid  Artery  for  Secondary  Hemorrhage.     (Ann.  Surg.,  1890,  v.  12,  p.  110-24.) 
Rupture    of    Middle    Meningeal    .Artery    Without    Fracture;     Ligature    of    Common 
Carotid   Artery    for   Secondary   Hemorrhage.      ( Tr.   .\m.    Surg.   .\ss.,    1890,   v.   8, 
p.  167-79.) 
Tuberculous  Disease  of  the  Tarsus.     (J.  Med.  Coll.  of  Ohio,  1890,  v.  1.  p.  8.")-88.) 
Tuberculous  Diseases  of  the  Tarsus.     (Med.  News,  Phila.,  1890,  y.  .")7.  p.  ■■i(i4-(i7.) 
\'aginal  Cystolithotomy  in  a  Child.     (J.  Med.  Coll.,  Ohio,  1890,  v.  1,  p.  41.) 
Abscess  of  Liver;  Hepatotomy.     (J.  Med.  Coll.  of  Ohio,  1890-91,  v.  1,  p.  111.) 

1891 

.Aneurism    of    the    Femora!    .Artery;    Deligation    of    the    Superficial    Femoral;    Cure. 

(J.   Med.   Coll.  of   Ohio.    1891,   y.   2,   p.   -V     Also   Cin.    Lancet-Clinic    1.891,   v.   20, 

p.  o29-;31.) 
Pistol-Shot  Wounds  of  the  Brain.     (Cin.  Lancet-Clinic,  1891.  v.  27.  p.  .Vi7-(il.) 
Linear  Craniotomy  for  Microcephalus.     (Med.  News,  June  13,  1891.) 
Ruptur    der    .Arteria    meningea    media    ohne    Fractur;    Ligatnr    der    Arteria    carotis 

communis  bei  secundarer  Blutung.     (Arch.  f.  Klin.  Chir.,  1891,  \-.  42,  p.  229-:!0. ) 

1892 

Management  of  the  Gangrenous  Hernia.  With  Report  of  a  Case.     (.1.  .Am.  Med.  .Ass., 

1892,  V.  19,  p.  198.) 
Traumatic  Aphasia.     (Ohio  Med.  J.,  1892.  v.  -i,  p.  41-4:>.) 

Treatment  of  the  Gangrenous  Hernia.     (.Ann.  of  Surg.,  18!t2,  v.  lii,  p.  .'i.'ili-.Sl.) 
Trephining  for  Abscess  of  the  Brain.     (Cin.  Lancet-Clinic.  1892.  v.  29.  p.  Oilii-7:!.) 

1893 

Empyema.     (Tr.  Ohio  Med.  Soc.  189:'..  p.  28.-.-9:3.     Also  Cin.  Lancet-Clinic,  189.1,  v.  31. 

p.  150-.-,4.) 
Recurrent   .Appendicitis;    Laparotomy:    Fecal    Concretion,    With    Bullet    for    Xucleus. 

(Ohio  Med.  J.,  1893.  v.  4,  p.  2:io.) 
Report  of  a  Case  of  .Appendicitis.     (Cin.  Lancet-Clinic,  189:i,  v.  :>0,  p.  07").) 

1894 
Extirpation  of  Aneurisms.     (.Ann.  of  Surg.,  1894.  v.  19,  p.  78-84.) 

Thyroid  .Abscess,  Thyroidectomy;  Recovery.     (.Ann.  of  Surg..  1894,  v.  2o,  p.  4O0-41:!.) 
Strangulated  Hernia  Gangrene  of  the  Intestine.     (Ohio  Med.  J..  1894,  May.) 
Treatment  of  Strangulated  Hernia.     (J.  Am.  Med.  Ass..  1894,  v.  23.  p.  20-20.) 

1895 

Concerning  Stone  in  the  Kidney,  and   Its  Operative  Treatment.      (J.  .Am.   Med.  .Ass., 

!8!r,.  V.  25,  p.  1-7.) 
Injuries  and   Diseases  of  the   Neck.      (Encvcl.   Sur.g.    (.Ashhurst.   N.   Y.).   189."),   v.  7, 

p.  7.M-82.) 


PUBLICATIONS   OF   DR.   JOSEPH   RANSOM  OFF 


Nature  and  Treatment  of  Glands  of  the  Neck.     (Med.  Fortnightly.  189.",,  v.  8,  p.  470.) 
Pelvic  Reflexes  in  the  Male.     (Med.  Prn-rcss,  ISICi,  v.  11.  p.  'jni-(il,) 
Pelvic  Reflexes  in  the  Male.     I  .Am.  j.  ..I  ()h^t.,  ls!i.-,,  v.  :11,  ]).  il7.-,-7!l.) 
Sarcoma  of  Bone.     (Ohio  Med.  J..  ISii.',,  v.  (i,  ii   ■_'■>  .'.ii. ) 
Tuberculosis  of  the  Neck.     (Ohio  Medical  Journal,  IS!).",,  p.  17l'-74.) 

1896 

Large    Parosteal    Fibro-Sarcoma    of    the    Thigh.     (.Annals    of    Surgery.    ]8!l(i,    v.    24, 

p.  188-195.) 

(Whitaker,   Ransohoff  and  Kramer)  ; 
Paraplegia :  Gunshot  Wound  of  the  Spinal  Cord  ;  Bullet  Located  by  the  Roentgen  Ray, 

and  Subsequently  Extracted ;  Obstinate  Bed  Sores   Relieved  by  Constant   Stay  in 

the  Water  Bath  for  Three  Months.     (Inter.  Med.  Mag..  189(i-7,  v.  .5,  p.  (347-(i(i8.) 
Parosteal  Sarcoma  of  the  Femur;  Extirpation  With  Recovery.     (Tr.  Am.  Surg.  Ass., 

189(1.  V.  14,  p.  44:!-4.-,4.) 
Susceptibility  and  Immunity  to  Surgical   Infections.     (Ohio  Med.  Journal.  ]89li.  v.  7, 

p.  I(i9-172.) 
Surgical  Treatment  of  Tubercular  Lesion.     (Cin.  Lancet-Clinic,  189(1,  v.  30,  p.  (\'i.\-i't'u .) 
Ueber   Erinnerungstauschungen   bei    .\lkohol-Paralyse.       (Allg.   Zeitsrhr.    f.    Psychiat. 

etc.,  189(;-7,  p.  9:«-94:.!.) 
Operative    Treatment    of     Irreducible    Subcutaneous    Fractures.       (.Am.    Jour.    Med. 

Science,  1897,  v.  114,  p.  417-424.) 

1897 

Radical  Cure  Umbilical  Hernia,  by  Omphalectomy,     (Med.  Rec,  l.'>97,  v.  ."il,  ji.  I."i(l-."i2.) 
Remarks  on  Operative  4>eatment  of  Irreducible  Dislocation  (jf  the  Shoulder.     (Ohio 
Med.    lournal.    Inne.   ls!(7.) 


Cancer  of  the  Bladder.     (Cin.  Lancet-Clinic,  189.S,  n.  s.  v.  41.  p.  0:!2.) 
Lympho-Sarcoma  of  the  Neck.     (Cin.  Lancet-Clinic,  1898,  n.  s.  v.  40,  p.  ()(I8-10.) 
Considerations   on    the    Diagnosis   and    Operative    Treatment    of    Gall    Stones.      (Cin. 
Lancet-Clinic.  189X.  n,  s,  \-.  4i»,  p.  9-".-l(il.) 

1899 

Decortication    of    the    Tongue,    in    the    Treatment    of    Lingual    Psoriasis.      (.Ann.    of 

Surgery,  May,  18ft9.) 
Nephrectomy  Versus  Nephrotomy.     (Tr.  Am.  Surg.  ,\ss.,   189!t. ) 

1900 

Our  Students  and  Their  Teachin.g.     (Cin.  Lancet-Clinic,  190(1.  n.  s.  v.  44.  p.  479-48(1.) 
Specimen  of  Vesical  Calculus.     ((I'in.  Lancet-Clinic,  19(iii,  n.  s.  v.  4-'i,  ]).  (!l."i-l(i.) 

1902 

Trephining  for  Brain  Tumors;  Report  of  Two  Successful  Cases,  One  of  Nine  Years. 
(J.  of  Am.  Med.  Ass,.  19(12.  v.  :!9,  p.  9(1:1-0(1.) 

1903 

(Ransohoff,  J.,  and  Phelps,  A.  V.)  : 
An   Unusual  and   Fatal  Hemorrhage   from   Trephining.      (Tr.   Am.   Surg.  Ass.,   190.^, 

V.  21,  p.  563-568.) 
Zur  Aetiologie  der  akuten  hamorrhagischen  Encephalitis.     (Monatsch.   f.  Psychiat.  u. 

Neurol.,  190.<?,  v.  13,  Ergnzngshft,  p.  440-48.) 
Hepatectomy  Tuberculoma  of  the  Liver.     (Tr.  South.  Surg.  &  Gynec.  .Ass.,  19(t3;  1904, 

V.  10,  p.  403-10.    Also  Med.  News,  1904,  v.  84,  p.  727-7.30.) 


Paije  0 


RAXSOHOFF  MFMORIAL  VOLUME 


Syphilis   am    Auge.      (Festsclir.   z.    1st.    Cong.   d.    Deutsch.    Gesellscli.    z.    Bekampf.   d. 

Geschlechtskrankh..  19(«,  p.  l;W-:U.) 
Uniliteral  Disease  of  the  Kidney  Simulating  Stone.     (J.  of  Am.  Med.  Ass.,  1903,  v.  -10, 

p.  1502-04.    Also  Tr.  South.  Surg.  &  Gynec.  Ass.,  1002;  100:!.  v.  !"),  p.  :W4-70.) 

1904 

Stone   in   the   Kidney,   Its   Diagnosis   and   Operative   Treatment.      (Med.   News,    1904, 

V.  K.-,,  p.  1(111-1.-..) 

1905 
Gangrene  of  the  Gall-Bladder.     ( Tr.  South.  Surg.  &  Gynec.  Ass.,  190.-,.) 
Renal  Calculus  Removed  from  Ureter.     (Lancet-Clinic,  19n.->.  n.  s.  v.  -A,  p.  .j.-)8.) 
Thyroidectiimy   in   the   Treatment   of   Exophthalmic   Goitre:    With    Report   of    Cases. 

(Lancet-Clinic,  19ii.-|.  n.  s.  v.  •->4,  p.  07:5-78.) 

1906 
Cancer  of  the  Stomach  from  the  Surgeon's  \'ievvpoint.     (  Lancet-Clinic,  19ii(i,  n.  s.  v.  .".(^ 

p.  0-2.-.---'9.) 
Case  of  Sarcoma  of  Head  of  the  Tibia.     (Lancet-Clinic,  1900,  n.  s.  v.  -Mi,  p.  69^..) 
Discussion  of  the  Pleura  in  the  Treatment  of  Chronic  Empyema.     (Ann.  Surg..  1900, 

V.  4:3,  p.  502-11.) 
Cancer    of    the    Stomach    from    the    Surgeon's    Viewpoint.      (Abstr.    Ohio    Med.    J., 

1906-7,  V.  2,  p.  l(i2-0.-,. ) 
Gangrene  of  the  Gall  Bladder.     (Tr.  South.  Surg.  &  Gynec.  Ass..   i;)o.-.;   Phila.,   1900, 

V.  18,  p.  48-68.) 
Gangrene  of  the  Gall  Bladder,  Rupture  of  the  Conuuon  Bile  Duct.  With  a  Xew  Sign. 

(J.  Am.  M.  Ass.,  1906,  v.  4(1,  p.  :M5-97.) 
Pulsating   Exophthalmos;    Ligature   of   the   Common    Carotid,    External    Carotid   and 

Superior  Thyroid  Arteries.     (Surg.  Gynec.  &  Obst.,  1906,  v.  '■'>,  p.  19:!-9.->.) 
Rupture  of  the  Common  Duct  With  an  Unusual  Sign.     (Tr.  South.  Surg.  &  Gynec. 

Ass.,  1905 ;  Phila.,  1906,  v.  18,  p.  .50-68.) 
The  Treatment  of  Fractures  of  the  Patella.     (J.  .\m.  ^L  .Ass.,  l»0(i,  v.  47,  p.  1177-81.) 

1907 
Die  Behandlung  der  Patellarbruche.     (Klin.  Therap.  Wchnschr.,  1907,  v.  14,  p.  127-36.) 
Cirrhotic   Liver,  With   -Ascites   and   .Albuminuria ;   Talma   Operation   Performed,   Fol- 
lowed bv  Relief  of  .Ascites  and    Albuminuria.      (Lancet-Clinic,   1907,  n.   s.  v.  58, 
p.  3.55.)  ■ 
Very  Large  Recurrences  .After  Operation  for  Carcinoma  of  the  Breast.     (.Ami.  Surg., 

1907,  V.  46,  p.  72-80.) 

Very   Late   Recurrences   .After   Operation    for   Carcinoma    of    the   Breast.      ( Tr.    .Am.' 
Surg.  Ass.,  19(17,  v.  25,  p.  187-95.) 

1908 
A  New  and  Rapid  Method  of  Perineal  Drainage  in  Suprapubic  Prostatectomv.     (J.  Am. 

M.  Ass.,  1908.  V.  51,  p.  887-9(i. ) 
Surgery  of  the  Kidney,  the  Ureter  and  the  Suprarenal  Glan<!.     (  Syst.  Surg.   (Keen), 

1908,  V.  4,  p.  18:!-271.) 

Venous  Thrombosis  and  Hydrocele  of  the  Inguinal  Canal.     (.\nn.  Surg.,  1908,  v.  48, 
p.  247-.57.    Also  Tr.  South.  Surg,  &  Gynec.  Ass..  1907;  Phila.,  1908,  v.  2o,  p.  406-17.) 


Gunshot  Injury  of  the  Brain,  With  Late  Manifestations  .After   Inmiediate   Recovery. 
(Ann.  Surg.,  1909,  v.  -50,  p.  66-72.    Also  Tr.  Am.  Surg.  Ass.,  l!Hi9.  v.  27,  p.  586-94.) 
Renal  Surgery.     (Toledo  M.  &  S.  Reporter,  1909,  v.  :35,  p.  49-55.) 


PUBLICATIONS   OF   DR.   JOSEPH   RANSOHOFF 


Kidney  Surgery— Oration.     (Ohio  State  M.  J.,  Jan.,  1900.) 

Inter-Ilio-Abdoininal   Amputation,  witli  Report  of  a  Case.     (-Ann.  Surg.,  lOoO,  v.   ")(•, 

p.  925-3.^.) 

1910 
The  Modern  Surgery  of  the  Kidney.     (West.  Virg.  M.  J.,  1910-11,  v.  ">,  p.  320;  i;3.) 
Pancreatic  Hemorrhage  and  Acute  Pancreatitis.     (Surg.  Gynec.  &  Obst.,  1910,  v.  10,  p. 

208.     Also  Ann.  Surg.,  1910,  v.  -M,  p.  070-81.) 
Pancreatic  Hemorrhage  and  Acute  Pancreatitis,  With  a  Report  of  Three  Cases.     (Tr. 

South.  Surg.  &  Gynec.  Ass.,  1909;  Phila.,  1910.  v.  22,  p.  112-2.-).) 
Prognosis  and  Operative  Treatment  of  Fracture  of  the  Base  of  the  Skull :  Based  on  an 

Analysis  of  190  Cases.     (Ann.  Surg.,  1010,  v.  -M,  p.  700-811.     ALso  Tr.  Am.  Surg. 

Ass.,  1910,  V,  28,  p.  560-77.) 

1911 

(Ransohoff,  J.,  and  Ransohofif,  J.  L.)  : 

Intrathoracic    Surgery    (Heart    and    Oesophagus    Excluded).      (Am.    Pract.    &    Surg. 

(Bryant  &  Buck),  1911,  ^..  8,  p.  :l-.j8.) 

1912 

The  Dissecting  Room:  Then  and  Now.     (Lancet-Clinic.  1912,  v.  107,  p.  420.) 
Gastro-Enteroptosis ;    When    Is    Surgery    Indicated?      (Surg.    Gynec.    &    Obst.,    1912, 

V.  15,  p.  21-27.) 
Ice  Tongs  Extension  for  Simple  Fracture  of  the  Femur.     (Tr.  Am.  Surg.  .\ss.,  1912, 

V.  30,  p.  706-38.    Also  Lancet-Clinic,  1912,  v.  108,  p.  179-82.) 
Median  Harelip.     (Lancet-Clinic,  1912,  v.  108,  p.  48.5-87.) 
The  Operative   Treatment  of   (jastro-Enteroptosis.      (Bost.   M.  &   S.  J.,   1912,   v.   107, 

p.  347-58.) 
Acute  Unilateral  Septic  Infarct  of  the  Kidney.     (Lancet-Clinic,  v.  1912,  107,  p.  58:1.) 
Suture  of  Bullet  Wound  of  the  Lung  with  a  New  Method  of  Closing  Pleural  Defects. 

(Lancet-Clinic,  1912,  v.  lf>7,  p.  517-19.) 

1913 

.\cute  Perforating  Sigmoiditis  in  Children.     (.Ann.  Surg.  1913,  v.  58,  p.  218-25.     Also 

Tr.  Am.  Surg.  Ass.,  1913,  v.  31.  p.  422-:!(i.) 
Fat  Hernia.      (Lancet-Clinic,   191.3,  v.   19,  p.  6-10.     Also  Tr.   South.   Surg.  &   Gynec, 

1912;  Phila.,  191:!,  v.  25,  p.  260-74.) 
Osteitis  Deformans,  Central  Sarcoma,  Streptococcus   Infection.      (Lancet-Clinic,   1913, 

V.  110,  p.  (i72-74.) 
What  Can   Surgery  Do   for  Gastro-Enteroplosis?      (Tr.   South.   Surg.  &  Gynec.  Ass., 

1912,  V.  24,  p.  5(i4-76  i  Discussion  |,  p.  500-002.) 

1914 

Heredity  in   Bone   Lesions,   With   the   RepiTt   of   an    Unusual   Family   History.      ( Tr. 
South.  Surg.  &  Gynec.  Ass.,  191:;;  Atlanta.  l!ill.  v.  20,  p.  10ii-7o.) 
(Ransohotf,  J.,  and  Kansohoff,   ].  L.)  : 
Radium  Treatment  of  Cancer.     (Lancet-Clinic.  1911,  v.  Ill,  p.  6ill-7o.) 

1915 
Pancreatic  Cyst  as  a  Cause  of  Unilateral   Hematuria  With   Report  of  a  Case.      (Tr. 

South.  Surg.  &  Gynec.  Ass.,  1915,  v.  28,  p.  lll)-2!l.) 
Status  of  Cerebral  Surger>'.     (Cin.  Lancet-Clinic,  1915.  v.  113,  p.  537-41.) 

1916 

Addresses  on  Daniel  Drake.     (Lancet-Clinic,  1910.  v.  115,  p.  599-ti09.) 
Angina  Ludovivi.     (Lancet-Clinic,  191(),  v.  115,  p.  4:il-:!4.) 


RAXSOHOfF  MEMORIAL  VOLUME 


Dislocation  of  the  Knee.     (.Lancet-Clinic,  liin;.  v.  llo,  p.  (i!l-7I.     Also  Tr.  West.  Surg. 

Ass.,  liU-J:  Minneap.,  191(i,  p.  Sl-90.) 
Pancreatic  Cyst  as  a  Cause  of  Unilateral  Haematuria  With  Report  of  a  Case.     (Surg. 

Gynec.  &  Obst.,  191(),  v.  -22,  p.  21?,.} 

(RansohofT,  J.,  and'Ransohoflf.  J.  L.^  : 
Radium  Treatment  of  Uterine  Cancers.     (Ann.  Surg.,   IHKi,  v.  W.  p.  •J!t,'<-:lii:!.     .Mso 

Tr.  Am.  Surg.  Ass.,  191(i,  v.  :14,  p.  202-12.) 
Radium  Treatment  of  Uterine  Fibroids.     (Lancet-Clinic,  lOlli,  v.   ll"i,  p.   llii-lS.) 
.•\  Simple  Method  of  Draining  Kmpycma.     (J.  .\m.  M.  Ass.,  IHH;.  v.  ilil,  p.  llDii.) 

1917 

Congenital   Lipomata  of   the   Cheek.      (.\nn.   Surg.,   1917,   v.   fi.".,   p.   711-U.     .Also   Tr. 

South.  Surg.  .\ss.,  191(1 ;  Phila.,  1917,  v.  30,  p.  65-69  [Discussion!,  p.  SH-S-V) 
Plastic- Surgery.     (Ref.  Handb.  .\Ied.  Soc,  1917,  v.  7,  p.  240-2.-)3.) 
Some  Considerations  in  Brain  Surgery.     (Interstate  Med.  J.,  1917,  v.  24,  p.  .■i4:l-:>:!.) 

1918 

Hemorrhage  from  an  .\neurism  of  the  Internal  Carotid  -Artery,  Following  Septic  Sore 
Throat.  (Ann.  of  Surgery,  UUS.  v.  liS,  p.  I'd-'i?,.  .\lso  Tr.  .\m.  Surg.  .\ss., 
1918,  V.  3(i,  p.  456-60.) 

On  Injuries  of  the  Cervical  Spine.  (Tr.  South.  Surg.  .\ss.,  191S,  v.  21,  p.  265-282. 
Also  Surg.  Gynec.  &  Obstet.,  191S,  v.  27,  p.  241-47.) 

Teaching  in  the  Hospital.     (  Interstate  M.  J.,  nU.S  v.  2--.,  p.  719-.V!.) 

1919 

Traumatic  Facial  Diplegia.     (.\nn.  of  Surgery.  1!I19,  v.  7ii,  p.  1.VI-.56.) 

1920 

Empyema   at   Cincinnati   General    Hospital    During   Influenza    Epidemic.      (J.   of   Am. 

Med.  Ass.,  192n,  v.  74,  p.  2.38.) 
Hyperplastic  Tuberculosis  of  Small  Intestine.    (.\nn.  of  .Sur^erv,  192",  v.  72.  p.  97-103.) 
John  Hunter.     (Cin.  Journal  of  Med.,  1920.) 

On  the  Borderland  of  Medicine  and  Surgery.  (  Med.  Bull.  University  of  Cin., 
Nov.,  1920.) 

EVA  G.  KYTE. 
AXXA  J.  DULING. 
MARGARET  MURRAY. 


THE  THERAPEUTIC  POSSHULITIES  OF  llLO(  )D  TRANS- 
FUSION—Mr<:TH()DS.  IXDICATIOXS  AND   R]<,SULTS* 

E.  R.  Arn,  M.  D.,  F.  a.  C.  S. 

Junior   Surgeon,   Miami   Valley   Hospital. 

HISTORICAL  CONSIDERATIOX, 

The  operation  of  blood  transfusion  is  an  ancient  one.  Mention  of  it 
may  be  found  in  early  medical  writings.  In  early  times  it  was  attempted 
by  using  blood  of  lower  animals.  It  was  not  until  after  the  discovery  of 
the  circulation  by  Harvey,  in  IfiZS,  that  it  was  taken  up  with  added  interest, 
as  well  as  along  scientific  and  rational  lines.  Dr.  J.  B.  Dennis,  professor  of 
physiology  at  the  University  of  Paris,  successfully  performed  the  first  trans- 
fusion of  human  blood  to  a  jiaticnt  in  ir-67.  This  was  done  by  means  of  a 
bone  canula.' 

The  Germans  used  defibrinated  blood  quite  extensively  in  the  early  part 
of  the  nineteenth  century.  But  because  of  the  dangers  of  intravesical  clot- 
ting, it  was  given  up,  and  use  of  saline  solution  substituted. 

The  modern  practice  of  blood  transfusion  may  be  said  to  have  had  its 
origin  in  1897,  when  Murphy  reported  his  method  of  blood  vessel  suture  in 
transfusion.  In  1906,  George  W.  Crile,-  reported  his  special  canula  for 
transfusion.    It  was  a  marked  advance  in  this  work. 

The  difficulties  and  objections  to  all  of  these  methods  were  the,  (a) 
wound  on  the  donor;  (b)  obliteration  of  important  blood  vessels;  (c)  and 
difficulties  encouiUered  in  technique. 

Further  investigation  developed  the  syringe  method,  Lindeman,^  the 
paraffined  tubes  of  Kimpfon  and  Brown* ;  the  syringe  method  of  Unger,^ 
and  finally  the  anticoagulants  of  Lewishon.'"'  The  simplest  as  well  as  the 
most  practicable  of  all  of  these  is  the  anticoagulant  or  Citrate  method,  and 
is  the  method  of  choice  in  the  majority  of  clinics  today. 

TF.CHXIQUE  OF  CITRATE   METHOD. 
The  citrate  method  is  the  inethod  in  general  use  today.     The  apparatus 
necessary  consists  of  the  following: 
1  Tourniquet. 

4  Intravenous  needles  (Kaliski  type). 
4  Pieces  of  rubber  tubing,  12  inches  long. 
18  Grains  of  sodium  citrate. 
1  30  cc.  Graduate. 
1  500  cc.  Graduate. 
1   Glass  stirring  rod. 

1  Glass  cylinder  with  3  feet  of  rubl)cr  tubing. 

2  or  more  camliric  needles. 

•Read  t.rf,..    ll„     Si,,ti,,il    S.  >!>   n   „f  tl,e  Oliui   .Slali-   Mi-<lical    .\ssuriation.  during   tlic   Scviiily- 
Fon.ll.  .'ViiniKi:   Mirl.nt.-,  al   'l.,li.l...    |,i„<-  2,   1920. 

•From    Oliiu    Statu    Ikdical    Journal,    August,    1920. 


RANSOHOFh'  MILMORIAL  VOLUME 


The  citrate  solution  is  prepared  by  boiling  the  citrate  in  two  ounces  or 
60  cc.  of  sterile  distilled  water  for  two  minutes,  and  30  cc.  or  one  ounce  is 
placed  in  tlie  sterile  500  cc.  graduate  containing  the  sterile  glass  stirring  rod. 
The  intravenous  needle  is  introduced  into  the  vein  of  the  donor,  after  trans- 
fixing same  with  a  cambric  needle,  and  blood  is  allowed  to  flow  into  the 
500  cc.  graduate.  When  nearing  the  250  cc.  mark,  the  other  30  cc.  or  one 
ounce  of  citrate  solution  is  added,  and  blood  is  permitted  to  flow  until  there 
are  500  cc.  of  mixture.  If  more  blood  is  desired,  a  sufificient  amount  of 
citrate  solution  is  added  to  maintain  the  ratio  of  0.24  per  cent.,  or  30  cc. 
of  2  per  cent,  citrate  solution  for  each  250  cc.  of  blood. 

Should  clotting  occur  in  the  needle  of  the  donor,  it  should  be  immediately 
withdrawn  and  another  inserted. 

The  citrated  blood  is  then  transferred  to  a  suitable  flask,  and  permitted 
to  flow  into  the  vein  of  the  recipient,  very  slowly  at  first,  especially  for  the 
first  60  cc.  of  citrated  blood;  marked  slowing  of  pulse,  attacks  of  syncope, 
precordial  distress,  dyspnoea,  and  severe  pains  in  lumbar  region  are  danger 
signals,  and  transfusion  should  be  stopped  and  another  donor  secured.  Ex- 
cept in  acute  haemorrhage,  where  the  bulk  is  most  important,  500  cc.  of  mix- 
ture is  usually  all  that  is  re<|uircd  lo  stimulate  the  blnod-forming  organs  in 
chronic  conditions. 

IXDIC.-VTIOXS  Ol'  TR.WSFUSIOXS. 
Hard  and  fast  rules  cannot  be  drawn.  One  innst  he  i/iiided  by  the  single 
purpose  of  doing  the  most  good  with  the  minimum  risk.  I  hardly  think  that 
any  great  number  of  unnecessary  transfusions  are  carried  out,  but  I  am  con- 
vinced that  many  cases  are  lost  either  by  not  transfusing  at  all,  or  by  doing 
it  too  late.  And  not  only  this,  there  arc  many,  many  cases  zchose  illness  could 
be  materially  shortened  by  introduction  of  blood,  whose  operation  could  he 
viadc  less  hazardous,  and  whose  whole  aftercourse  could  be  made  less  bur- 
densome.   The  following  is  a  list  of  probable  indications: 

1.  Transfusions  for  actual  haemorrhage: 

(a)  Traumatic. 

(b)  Gastric  and  duodenal  ulcer. 

(c)  Post-partum. 

(d)  Ruptured  ectopic  pregnancy. 

(e)  Typhoid  haemorrhage. 

2.  Transfusions  in  connection  with  the  surgical  operations: 

(a)  Preliminary  to,  during  and  after  operation. 

(b)  For  post-operative  haemorrhage. 

(c)  For  post-operative  shock. 

(d)  For  post-operative  anaemia  and  ])r()stratiiin. 

3.  Transfusions  for  the  relief  of  liaemorrhagic  conditions. 

(a)  Purpura  haemorrhagica. 

(b)  Haemopilia. 


(c)   Haemorrhage  secondary  to  ( 1 )  blood  diseases,  (2)  severe  infec- 
tions, (3)  jaundice,  (4)  idiopathic  uterine. 

4.  Transfusions  for  blood  disease : 
(a)    Pernicious  anaemia. 

(c)   Leukaemia. 

5.  Transfusions  for  infections: 

(a)  Infections  with  pyogenic  organisms. 

(b)  Subacute  streptococcus  endocarditis. 

(c)  Subacute  infection  of  any  nature  other  than  septicaemia. 

6.  Transfusions   for  intoxication  and  poisonings: 

(a)  Toxaemia  of  pregnancy. 

(b)  Eclampsia. 

(c)  Uraemia. 

(d)  Benzol  poisoning. 

(e)  Illuminating  gas  poisoning. 

7.  Transfusions  for  debilitated  conditions: 

(a)  Cancer. 

(b)  Malnutrition. 

(c)  Simple  anaemia  from  any  cause. 

TRAXSFUSIOX  IX  REL.\TIOX  TO  H.XEMORRHAGE  AXD  OPER ATIOX. 

In  discu.ssing  class  one  and  two,  we  may  briefly  discuss  other  means  of 
controlling  haemorrhage.  Until  the  advent  of  blood  transfusion  in  a  prac- 
tical form,  there  was  no  dependable  reserve  remedy  in  the  physician's  arma- 
mentarium, so  far  as  great  blood  losses  were  concerned,  chief  among  these  is 
the  futility  of  drugs,  and  next  in  order  is  abuse  of  salt  solution.  (Ine  has 
only  to  consult  the  hospital  records  to  discover  how  profoundly  drugged 
were  most  patients  who  had  the  misfortune  to  bleed,  and  a  little  closer  study 
of  some  records  will  show  how  thoroughly  waterlogged  by  salt  solution  they 
were  in  addiHon. 

It  should  be  generally  understood  that  if  the  bleeding  has  not  been  too 
great,  a  few  hundred  cc.  of  salt  solution  are  all  that  is  needed  to  tide  a 
patient  over  a  dangerous  period.  In  cases  of  very  severe  haemorrhage,  thc 
amount  may  be  increased  a  bit,  but  if  1000  to  1500  cc.  of  solution  do  not 
steady  a  falling  blood  pressure,  or  cause  a  slight  rise,  its  introduction  had 
better  be  discontinued.  Even  where  there  has  been  a  rise,  the  greatest  eau- 
tion  must  be  exercised,  for  be  it  remembered  that  in  these  desperate  condi- 
tions, salt  solution  will  frequently  cause  a  rise  in  blood  pressure,  but  li'ill 
not  sustain  it. 

Where  the  bleeding  has  been  e.vcrssi-iw  a  transfusion  of  blood  is  indi- 
cated because  it  has  been  conclusively  sho-a'n  that  blood  alone  can  raise  a 
pressure  and  sustain  it.  .S'alt  solution  has  no  siislaining  power,  per  se,  and 
when  the  fall  comes  after  a  rise  from  this  means,  it  usually  protends  the  end. 
for  added  salt  solution  is  useless.     It  ncrer  raises  a  pressure  t'wice. 

Page  ir, 


RAXSOItOFF  MEMORIAL  VOLUME 


As  the  result,  then,  of  blood  transfusion,  we  have  been  able  to  really 
study  the  phenomenon  of  haemorrhage  for  the  first  time,  and  we  have 
learned  the  value  of  doing  as  little  as  possible  in  the  condition.  Rest,  quiet, 
attempts  to  check  the  bleeding  by  mechanical  means,  an  ice  bag  over  or  near 
the  site  of  bleeding  as  possible,  a  bit  of  morphine  for  the  restlessness  occa- 
sioned by  the  condition,  and  salt  solution,  and  we  have  the  entire  armamen- 
tarium for  treating  bleeding.  For  we  have  learned  that  the  body  itself  does 
more  towards  checking  haemorrhage  than  can  be  done  by  outside  means, 
by  automatically  lowering  its  own  blood  pressure,  and  thereby  causing  a 
slowing  of  the  circulation  and  renewed  opportunity  for  coagulation  of  the 
blood  at  the  site  of  leakage.  But  the  more  I  see  of  haemorrhage  and  anaemia 
in  general,  the  more  I  am  convinced  of  the  utter  futility  of  having  a  specific 
rule  by  which  to  be  rigidly  governed.  Each  case  is  a  study  unto  itself;  each 
individual  represents  an  entity  which  must  be  judged  from  all  angles,  and 
experience  in  handling  the  condition  must  have  a  great  deal  of  weight  in  the 
ultimate  decision  as  to  the  course  to  pursue.  It  is  advisable  though  to  have 
some  tentative  plan  of  procedure  in  case  of  haemorrhage,  and  since  there 
are  certain  fundamental  features  common,  in  a  degree,  to'all  cases,  it  is  pos- 
sible to  formulate  a  working  rule.  For  instance,  a  sudden  loss  of  blood  is  a 
much  more  serious  matter  than  a  gradual  depletion,  and  a  rapidly  falling 
blood  pressure  is  always  a  warning  of  value,  though  it  must  be  remembered 
that  nausea  of  the  slightest  degree  will  af^'ect  this  phase  of  the  situation. 
But  these  two  features  really  are  dependable  guides  in  the  majority  of  in- 
stances, and  experience  has  demonstrated  that  a  good  working  rule  is  to 
transfuse  if  the  blood  /pressure  falls  as  km.'  as  seventy  mm.  of  mercury,  since 
life  is  hardly  possible  with  a  pressure  below  that  limit.  In  some  instances,  if 
the  physician  or  surgeon  in  charge  of  the  case  has  not  taken  the  steps  usual  in 
emergency  cases,  it  may  be  wise  to  delay  until  these  can  be  instituted,  prep- 
aration for  transfusion  being  made  in  the  inter\al.  If  the  actual  bleeding 
has  been  checked,  if  the  patient  is  quiet,  if  salt  solution  has  been  given  in 
the  proper  manner,  and  the  blood  pressure  still  remains  around  seventy, 
with  a  tendency  to  flutter  a  little  below  this  point,  it  ma_\-  be  assumed  that 
the  case  is  utterly  hopeless,  unless  new  blood  is  introduced,  ;ind  jjrocrasli- 
nation  at  this  stage  of  the  game  is  a  fearfully  dangerous  plan. 

Quoting  the  late  Lindeman."  "in  cases  of  haemorrhage,  blood  transfusion 
is  specific,  no  matter  how  e.vtreme  the  haemorrhai/e,  provided  some  life  is 
still  present.  There  is  no  condition  so  grave  from  haemorrhage  alone,  that  a 
patient  cannot  be  reri^'cd  by  blood  transfusion." 

Case  Xiimbcr .  ^h's.  H.  Diagnosis,  ectopic  pregnancy.  Was  ailmitu-d  to  hos- 
pital for  operation.  While  being  prepared,  was  seized  with  sharp  pain  in  left  side  in 
region  of  tube,  followed  rapidly  liy  fainting  and  collapse.  Pulse  imperceptible  at 
wrist.  Respiration  rapid,  air-hunger  marked.  Patient  semi-conscious.  Operation  was 
rapidly  performed  under  local  anaesthesia,  bleeding  vessel  secured,  left  tube  removed. 
Transfusion  was  started.  Patient  became  conscious  after  receivin.g  M)  cc.  of  blood, 
pulse  perceptil)le.  Was  given  all  told  l.(K)()  cc.  of  blood  itom  Group  II.  donor,  patient 
being  in  Group  II.  Pulse  120  on  leaving  table,  and  made  good  recovery. 
Page  m 


E.  R.  ARN 


TRANSFUSION'  FOR  HAEMORRHAGIC  CONDITIOX. 

Transfusions  for  haemorrliagic  conditions  comprise  a  group  of  unknown 
etiology,  and  whose  treatment  in  the  i)ast  have  run  the  entire  gamut  of 
tlierapeutics.  In  Purpura  Haemorrhagica,  the  results  of  transfusions  arc 
only  fairly  good.  Repeated  small  transfusions  are  often  necessary  to  con- 
trol bleeding. 

Haemophilia  is  not  cured  by  transfusion,  but  for  the  bleeding  of  haemo- 
philia it  is  practically  a  s])ecific.  It  will  succeed  when  all  other  methods  fail. 
Valuable  time  should  not  be  lost  in  attempts  to  control  bleeding  by  other 
methods,  since  we  have  at  our  command  a  specific  that  will  not  only  control 
bleeding,  but  replace  the  blood  lost.''  , 

In  bleeding  nf  the  new-horn,  transfusion  is  a  sf^ecific.  Jii  aliutisl  exsuii- 
(jiiinated  infant,  ton  7('eak  to  ery  and  in  a  dying  state,  is  transformed  inune- 
diately  into  an  apparenll\  lieidlJiy.  rosy  and  crying  baby.  As  in  haemophilia, 
it  will  save  the  li\es  of  ilmsc  who  are  not  helped  by  subcutaneous  injections 
of  serum  or  blood.  Temporizing  by  using  less  effective  measures,  may  cost 
the  baby's  life.  This  is  especially  true  in  cases  of  melena  neonatorum,  which 
are  the  most  serious,  because  we  do  not  know  just  when  the  haemorrhage 
began,  or  how  much  internal  haemorrhage  is  taking  place.  Just  as  soon  as 
the  diagnosis  of  bleeding  from  the  stomach  or  the  bowel  of  the  new-born  is 
made,  transfusion  should  be  performed. 

In  jaundice,  where  the  coagulation  lime  is  delayed,  a  transfusion  will 
lessen  the  danger  of  bleeding.  In  cases  of  obstruction  of  the  common  duct, 
even  of  long  standing  with  marked  jaundice,  operation  may  be  successfully 
performed  without  haemorrhage  or  oozing,  if  a  prophylactic  transfusion  has 
been  made 

Case  No. .     Mr.  H.,  age  60.     Jaundice  of  eight  weeks'  standing.     History  of 

repeated  attacks  of  gall-stone  colic.  Jaundice  followed  last  attack  ..f  olic.  Was 
given  a  prophylactic  transfusion  of  3E0  cc.  of  blood,  and  oper.itnl  a(  end  i.f  .24  Imurs. 
Several  stones  were  found  in  the  common  duct,  as  well  as  in  K-ill-hkuldir-  X'l  oKjre 
than  ordinary  bleeding  during  operation:  no  oozing  following,  diagulation  time  before 
transfusion  15  minutes.     Patient  in  Group  II.,  and  donor  in  Group  IV. 

TRANSFUSION  FOR  BLOOD  DISEASES. 
Transfusion  for  blood  diseases  of  this  class,  viz.,  pernici(>us  anaemia  and 
leukaemia,  may  be  a  life-saving  measure  in  prolongation  of  the  life  of  the 
individual.  /;;  pernieioiis  anaemia,  transfusion  yields  results  superior  to  any 
other  mode  of  thera/^y.  Prcquently  it  acts  as  a  life-saving  measure  by  initiat- 
ing the  onset  of  a  remission.  There  is  no  evidence  that  the  disease  may  be 
cured  by  this  method.  Repeated  transfusions  may  be  necessary,  but  the  lives 
of  many  of  these  individuals  can  be  made  useful  for  years.  They  should  all 
be  grouped,  and  have  at  their  command  suitable  donors.  Small  doses  of 
blood  seem  to  bring  about  a  remission  as  quickly  as  large  doses.  Some 
donors  seem  to  accentual c  a  remission  sooner  than  others.  In  these  cases 
the  same  donor  should  be  UM'd  for  sulisci|uenl  transfusions,  as  the  dose  of 
blood  need  not  be  large. 


RAXSOHOff  MEMORIAL  VOLUME 


A  small  percentage  of  eases  of  pernicious  anaeina  do  not  respond  to 
transfusions,  tlicy  being  of  the  so-called  acute  -i'ariety. 

Case  illustrating  tlie  so-called  chronic  \ariety  is  as  follows: 

Case  No.  .     IMr.  W.,  aged  52.     Diagnosis,  pernicious  anaemia.     Hcinoglobin 

28  per  cent,  Sahli.  Group  II.  1,  950,000  R.  B.  C.  Many  normoblasts  marked  poikilocy- 
tosis,  dyspnoea  and  palpatation  on  least  exertion.  Began  to  feel  weak  18  months  ago. 
and  had  to  quit  his  occupation  one  year  aao.  TIail  licen  in  bed  most  of  the  time  for 
past  two  months.  Was  given  300  cc.  ni  I.Imi.iI  at  intervals  of  one  week  Group  IV. 
donor,  for  three  doses.  Marked  impmv  i  nu  iit  after  lirst  transfusion  as  evidence  by 
Hb.  40  per  cent  Sahh.,  increasing  appctitr,  il\>iiiic'ca  and  palpatation  less  marked. 
Hb.  55  per  cent  after  second  transfusion,  and  was  able  to  walk  three  squares  to  barber 
shop.     Returned  to  his  home  in  northern  part  of  state  after  third  transfusion. 

In  acute  lymphatic  leukaemia,  only  a  temporarily  favorable  effect  can 
be  secured  by  transfusion,  even  though  we  w^ithdraw  a  large  amount  of  blood 
by  phlebotomy  and  make  use  of  a  massive  transfusion  obtained  from  two 
donors,  or  employ  repeated  transfusions,  or  carry  out  transfusions  very 
early  in  the  disease. 

TR.WSFUSIOX   IX   IXFECTIOXS. 

Our  greatest  possibilities  for  research  lie  in  Class  \'.,  or  the  sub-acute 
and  chronic  infections.  It  has  been  fully  demonstrated  by  clinical  evidence 
that  transfusions  in  localized  pyogenic  infections  will  increase  the  patient's 
vitality  and  aid  in  overcoming  the  infections. 

In  bacteraemia,  when  the  source  of  the  organisms  can  be  found  and  elim- 
I'nated,  the  results  are  excellent,  as  in  cases  of  sinus  thrombosis  following 
mastoiditis,  in  which  the  jugular  has  been  ligated. 

Many  of  oiu-  long,  drawn  out  cases  of  appendiceal  abscess  ami  empyeniia 
would  be  materially  shortened  Ijy  small  therapeutic  doses  of  new  blood. 
Examples  of  this  class  are  the  following : 


Case  Xo.  .     IMr.  D.     Diagnosis,  secondary  anaemia;  Hb.  ,^5  per  cent,  R.  B.  C. 

2,500,000.  Operated  three  months  previous,  at  which  time  a  left  nephrectomy  was 
done  for  pyonephrosis,  secondary  to  renal  calculus.  Patient  has  made  a  very  slow  and 
discouraging  recovery.  Has  been  unable  to  work,  and  was  confined  to  his  home.  Was 
given  350  cc.  of  blood,  and  ten  days  later  300  cc.  more.  .After  second  transfusion, 
patient  was  able  to  be  up  and  care  for  himself.  Returned  to  his  home  feeling  stronger, 
and  with  a  Hb.  index  of  65  per  cent. 

Case  Xo. .    Miss  A.    Diagnosis,  chronic  empyeniia.    Cavity  of  eighteen  months 

duration,  holding  about  40O  cc.  Operated  second  time;  Modified  Shede  operation, 
patient  weak,  pulse  116  to  120,  and  wound  discharging  large  amount  of  pus.  Was 
.given  a  therapeutic  dose  of  300  cc.  of  blood,  .\fler  two  days,  patient  said  she  felt 
much  stronger,  wound  began  to  sliow  healthy  granulation,  discharge  liecame  less  in 
amount,  and  pulse  rate  fell  to  ^8. 

Other  examples  abound,  but  these  are  sufficient  to  indicate  the  necessity 
of  an  awakening  on  the  part  of  surgeons  to  certain  definite  deficiencies  in 
their  handling  of  anaemic,  debilitated  states  secondary  to  chronic  infections. 
If  a  person  suffers  a  sudden  loss  of  a  great  volume  of  blood,  we  make  up  the 
deficiency  by  adding  fresh  blood.  Why,  then,  do  we  not  likewise  in  the  many 
secondary  anaemias,  that  also  suffer  blood  los.ses,  but  in  smaller  amounts 
and  over  longer  periods?  I  have  transfused  a  few  of  these  chronics,  and 
the  new  blood  has  done  more  to  restore  hope  and  sleep  and  appetite  than 

Page  IS 


E.  R.ARN 


weeks  of  rest  and  barrels  of  iron  and  arsenic.  I  do  not  decry  these  neces- 
sary adjuvants  in  the  least ;  on  the  contrary,  I  advise  their  constant  use,  and 
have  seen  splendid  results  obtained.  I  merely  deprecate  and  condemn  their 
promiscuous  employment  in  conditions  beyond  their  therapeutic  reach.  They 
can  do  a  certain  amount  of  good,  but  in  many  cases  they  are  absolutely 
worthless,  and  in  many  of  these,  one  or  more  blood  transfusions  will  almost 
produce  a  miracle,  after  which  the  drug  and  rest-therapy  may  be  judiciously 
resumed.    This  has  been  proved,  but  has  not  been  recognized. 

TR.VNSFUSION  FOR  POISOXING. 

Transfusions  in  this  class  are  still  in  the  experimental  and  research  slage, 
except  for  poisoning  from  illuminating  gas. 

This  was  one  of  the  early  fields  for  blood  transfu.sii.ins,  and  consists  of 
blood  letting  and  blood  giving.  These  cases  are  usually  bled  700  to  1000 
cc.  and  then  transfused  a  similar  amount.'" 

Cases  in  Class  \l\..  are  really  a  repetition  of  conditions  described  earlier 
in  this  paper.  Kerley,  in  a  recent  article,  has  advised  small  transfusions 
in  certain  non-specific  types  of  Marasmus.  He  usually  gives  several  doses 
(jf  not  over  30  to  50  cc.  at  intervals  of  five  to  seven  days. 

D.^XGERS  OF  BLOOD  TRANSFUSION'. 
The   dangers   from  blood  transfusions  can   be  easily   avoided,   and   the 
operation  made  perfectly  safe  by  avoiding  the  following: 

(a)  Use  of  incompatible  blood. 

(b)  Excessively  large  transfusions. 

(c)  Emboli  of  air  or  blood  clot. 

Incoiiipatibilitv  of  Donor's  Blood:  Moss"  has  shown  the  presence  in 
human  blood  of  iso-agglulins  and  iso-hemolysins.  These  substances  will 
cause  agglutination  and  hemolysis  of  the  red  cells  when  incompatible  bloods 
are  mixed.  Moss  found  that  agglutination  frequently  occurs  without  hemo- 
lysis, but  that  hemolysis  is  always  associated  with  agglutination.  Human 
beings  can  be  divided  into  four  grou]is,  depending  upon  agglutins  present 
in  serum,  and  the  capacity  of  cells  to  agglutinate.  Ha  transfusion  is  to 
be  safe,  both  the  donor  and  the  recipient  should  belong  to  the  same  group, 
or  cells  of  the  donor  should  not  be  agglutinated  by  serum  of  the  recipient. 

These  groups  are  permanent  in  their  characteristics,  and  depend  upon 
the  Mendelion  laws  of  inheritance. 

The  following  are  the  four  groups  with  the  percentage  of  indixiduals  in 
each  group : 

Group  I.,  10  per  cent,  of  all  individuals  contain  no  agglutins. 

Group  H.,  43  per  cent,  of  all  individuals  contain  agglutin  .\. 

Group  HI.,  7  i^er  cent,  of  all  individuals  contain  agglutin  1!. 

Group  I\'.,  40  per  cent,  of  all  individuals  contain  agglutin  .\  and  B. 


KJXSOHOFF  MEMORIAL  J-QLUME 


RELATIONS  OF  THE  FOUR  BLOOD  GROUPS. 
Serum. 


Group : 

L 

n. 

IIL 

TV. 

,.1       L 

0 

X 

X 

X 

I. 

•S!     n. 

o 

o 

X 

X 

TL 

s ,     in. 

o 

X 

0 

X 

in. 

&i       IV. 

0 

0 

o 

o 

IV. 

^1 

I. 

IL 

in. 

IV. 

It  may  be  seen  that  no  serum  agglutinates  the  red  cells  belonging  to  its 
own  group,  but  will  agglutinate  and  may  hemolyse  corpuscles  of  other 
groups,  except  Group  I\'.  By  having  on  hand  serum  of  Group  II.  and  III., 
the  agglutinating  and  classifying  tests  are  easily  made,  not  reijuiring  over 
fifteen  minutes. 

We  have  made  it  a  practice  of  having  at  our  command  suitable  profes- 
sional donors,  properly  classified  through  physical  examinations,  and  with 
negative  Wassermanns.  They  can  all  be  readied  by  telephone,  and  are  paid 
a  fee  for  their  blood. 

By  having  this  grouj)  of  ])rofessional  donors,  ihe  time  of  making  the 
tests  is  greatly  lessened,  and  only  need  of  classifying  recipient  or  patient.  In 
emergency,  a  Group  lY.  donor  can  be  used  to  transfuse  any  other  class. 

(No    Asjsilutinins)  (1.     .\gylutinin   "B.") 

I  III 

10%    of    all    persons.  77c    of   all   persons. 


(1.      Agglutinin    "A.")  (  Both   .Agglutinins   ".\xB.") 

40%   of  all   persons.  43%   of  all  persons. 

II  IV 


MOSS  AGGLUTINATION  GROUPS. 

Essential  for  safety;  serum  of  recipient  should  not  agglutinate  corptis- 
cles  of  donor. 

If  you  do  not  have  professional  donors  suitably  classified,  it  is  always 
best  to  use  the  nearest  blood  relative. 

'i'he  second  danger  lies  in  transfusing  an  excessive  amount  of  blood. 
This  may  lead  to  embarrassment  of  circulation,  dilatation  of  the  heart  and 
and  pulmonary  oedema.  The  question  of  dosage  is  an  important  one  and  de- 
pends upon  several  factors:  age  of  individual,  condition  tor  which  trans- 
fusion is  indicated,  and  conditions  of  the  circulatory  apparatus,  especially 
the  inyocardium.  /;;  any  form  of  inyociirdial  dcraiujciiicnt,  if  transfusiofi 
ix  indicated,  small  amounts  should  be  given,  and  repeated  at  definite  inter- 
I'als,  to  avoid  invocardial  embarrassment. 


E.  R.  ARM 


Generally  speaking.  500  to  1000  cc.  is  the  usual  amount  transfused, 
except  in  the  blood  diseases,  in  which  250  to  350  cc.  seems  to  suffice  to  stim- 
ulate the  blood-forming  organs. 

Infants  under  six  months  of  age  receive  60  to  90  cc,  given  into  the  longi- 
tudinal sinus  or  jugular  vein. 

Danger  from  emboli  can  be  avoided  by  proper  technique.  In  using  citrate 
blood,  we  pass  the  blood  through  several  layers  (if  gauze. 

RE.^CTIONS. 

The  Mayo  clinic  reports  20  per  cent,  of  transfused  patients  to  have  some 
degree  of  reaction.  The  Crile  clinic  does  not  report  any  reactions,  believing 
them  to  be  due  to  improper  grouping.  Our  reactions  have  only  licen  two  in 
our  series,  and  both  were  due  to  faulty  grouping. 

The  case  and  siinplieity  of  the  citrate  method  of  trausfitsioii  i^'ill  siiij- 
ijest  an  increasing  number  of  indications  for  its  use.  JVlio  knuzcs.  hat  7<'hat 
some  of  the  acute  infections  may  be  treated  l>y  transfusions  of  small  thera- 
peutic (liises  of  blood  front  donors  immunized  b\'  the  disease,  or  b\  raceina- 
tion/ 

The  future  ;il(>ne  will  solve  these  Cjuestions.  As  stated  by  one  of  the 
investigators,  ihe  subject  of  blood  transfusions  has  thrilled  the  ini.-iginatiou 
of  man,  ever  since  the  discovery  of  the  circulation  of  the  blood.  In  the 
last  quarter  of  a  century  some  of  these  dreams  have  been  realized.  The 
difficulties  of  technique  of  the  old  methods ;  the  uncertainty  of  success  ;  the 
pain,  infection  and  life-long  scars  to  patient  and  donors ;  the  imi^ericisms  of 
its  therapeutics  relegated  its  use  to  the  court  of  last  resort. 

The  newer  method  of  blood  transfusion  makes  possible  new  applica- 
tions. They  open  up  a  new  field  of  therapeutics,  a  field  that  will  possibly 
solve  some  of  the  jircscnt  insoluble  enigmas  in  the  treatment  of  diseases, 
and  in  the  conservation  of  human  life. 

These  matters  are  not  caiialile  of  animal  experimentation,  and  I  cannot 
do  more  than  suggest  these  possibilities  to  the  medical  men  to  develop  them. 
The  time  has  arrived  when  we  should  seriously  begin  to  study  blood  dos;ige 
and  therapy. 

CONCLUSION. 

1.  Salt  .solution  will  never  raise  a  blood  pressure  the  second  time. 
Transfusion  of  blood  alone  will  save  the  patient. 

2.  The  Citrate  Method  is  the  method  of  choice,  because  of  the  ease  of 
application  and  preservation  of  important  blood  vessels  for  future  trans- 
fusions, or  other  intravenous  therapy,  should  occasion  require. 

3.  Transfusion  is  a  specific  for  haemorrhage  of  the  new-born.  In 
haemorrhagic  diseases  it  will  replace  blood  loss,  stop  the  haemorrhage,  but 
not  cure  the  condition. 

4.  Transfusion  saves  delay  and  decreases  morlalitv  in  cases  with  sec- 
ondary anaemia  requiring  operation,  as  fibroid  tumors  and  jaundice. 

Paye  HI 


RAXSOHOFF  MEMORIAL  VOLUME 


5.  Transfusion  of  blood  opens  a  new  field  of  therapy  in  the  treatment 
of  chronic  infections. 

6.  IVIost  reactions  can  be  averted  by  making  correct  group  tests,  and 
transfusing  from  the  same  group,  except  in  extreme  emergencies,  when 
Group  I\'.  may  be  used  without  grouping.  In  a  series  of  one  hundred  cases, 
our  reactions  have  been  6  per  cent.,  and  4  per  cent,  due  to  mistakes  in 
grouping. 

DISCUSSIOX. 
Dr.  LiTEiER  p.  HoWKLL.  Columbus :  I  wish  to  mention  the  facihty  with 
which  transfusion  can  be  done  in  infants  before  closure  of  the  anterior 
fontanelle.  As  you  recall  the  superior  longitudinal  sinus  anteriorly  is  located 
directly  in  the  median  line  although  at  the  posterior  fontanelle  it  lies  to  the 
right.  If  the  needle  be  introduced  just  anterior  to  the  posterior  angle  of  the 
anterior  fontanelle  and  directed  backward  at  an  angle  of  45  degrees  with  the 
interparietal  suture  to  a  depth  of  about  one-sixteenth  of  an  inch,  the  point 
of  the  needle  will  not  impinge  upon  or  injure  the  walls  of  the  sinus,  as  it  lies 
near  the  center  of  the  lumen.  The  precaution  must  be  made  to  keep  the 
hand  supporting  the  needle  tightly  steadied  against  the  head  and  to  inject 
the  blood  relatively  slowly.  Furthermore,  in  haemorrhage  disease  of  the 
new4iorn  it  is  necessary  to  type  the  blood,  if  that  of  the  father  be  given  and 
the  use  of  onlv  a  small  amount  is  necessary. 


Dennis.   T.  P..:     Pliilos.  Transact..  June  2S.   lf.t.7. 

Crile.  G.   W.:     Proc.   Soc.    E-Ni.er.   Bi„l.  an.i   .\led.. 

\ol  IV.. 

p.  0-8  Haemo 

rrhagt 

C.   Y..    1909. 

Lindman,  E. :     Amer.  .Tour.  Dis.  Child,   1913,  \o\ 

VI.,  p.  2 

!8-32. 

Kimpton.  .\.  R..  and  Brown.   T.  H.:     Jour.  .\.  M. 

A..  1913. 

Vol.  IX  I.  p. 

117. 

Un«r.  L.:     Journal  A.  M.  .\..  1915.  Vol.  IXIV.. 

p.  582. 

Lewishon,  R.:     Medical  Record,  Jan.  23.   1915. 

Blood  Transfusion.   Haemorrhage  and  the   .\nemia 

s:     Bernh 

ei,n.   J.    P.,    I. 

ippinc 

Lindeman.   E. :     Journal  -A.   M.   -A..   1919. 

Ungcr,  L.:     Journal   A.  M.   .\.,   .August,   1919. 

I,andois,  I.:     Die  Transfusion  des  Blutes,  Berlin. 

1911. 

Moss,  W.  L.:    Johns  Hopkins  Hosp.  Bull.,  1910, 

Vol.  X.\I. 

,   p.   1.3/0. 

Pemberton,  J.  D.,  Mayo  Clinic,  \ol.,  1918. 

OBSERVATIONS  UPON  SCARLET  FEVER.  DIPHTHERIA.  AND 
MEASLES  AT  THE  CINCINNATI  CONTAGIOUS  HOSPITAL.* 
By  Ar.EivRT  J.  V,p.u.,  A.  P.,  M.  D., 
Visiting  Staff,  Contagious  Group,  Cincinnati   Hospital. 

Although  there  are  number.s  of  good  men  who,  patiently  and  persever- 
ingly,  are  working  in  their  laboratorie,s  and  wards  upon  the  problems  which 
our  contagious  diseases  present,  and  the  results  of  their  efforts  a]>pear  at 
intervals,  one  is  impressed  with  the  comparatively  little  written  upon  the 
subject.  I  refer  in  this  paper  only  to  scarlet  fever,  diphtheria,  and  measles. 
This  may  be  due  to  a  placid  conclusion  on  the  part  of  many  that  our  text- 
books have  settled  the  clinical  signs  and  symptoms  and  that  repeated  failures 
along  etiological  and  bacteriological  lines  yield  little  of  promise  for  the 
future.  This  I  think  is  incorrect  and  someone's  persistent  eiYorts  will  event- 
ually be  crowned  with  success. 

Scarlet  fever  appears  variously  disguised,  probably  more  so  than  any 
other  contagious  disease,  and  if  we  can  find  out  practically  for  ourselves 
that  we  have  in  the  past  laid  too  much  stress  upon  certain  so-called  classical 
signs  and  not  enough  upon  others  and  that  a  rearrangement  of  some  of  our 
ideas  seems  advisable,  we  may  be  helped  to  an  earlier  recognition  and,  there- 
fore, a  luore  prompt  isolation  and  treatment  of  this  atifection.  During  the 
last  year  in  the  contagious  hospital  we  have  had  an  excellent  opportunity  for 
studying  this  disease  especially,  and  it  is  my  desire  to  furnish  statistics  as 
we  found  them  in  this  and  the  other  diseases,  with  certain  observations  which 
were  made  concerning  clinical  manifestations,  laboratory  findings,  and  treat- 
ment. 

Observations  were  made  upon  over  300  cases  of  scarlet  fe\cr.  The 
following  summary  indicates  in  percentage  form  our  findings  in  the  so- 
called  classical  symptoms  and  diagnostic  signs : 

Scarlet  fever,  315  cases.  Onset  with  vomiting,  50  per  cent.;  onset  with 
headache,  4  per  cent. ;  onset  with  sore  throat,  65  per  cent. ;  eruption,  whole 
body,  46  per  cent. ;  eruption,  partial,  35  per  cent. ;  mouth  pallor,  57  per 
cent. ;  rash  on  soft  palate,  38.6  per  cent. ;  membrane  on  tonsils,  29  per  cent. ; 
papill?e  enlarged,  56  per  cent.;  glazed  tongue,  17.7  per  cent.;  anterior  cer- 
vical glands  enlarged,  95  per  cent.;  submaxillary  glands  enlarged,  72  per 
cent. ;  eruption  gone  from  body,  five  and  one-half  days;  desquamation  began 
in  six  and  three-quarter  days;  blood  count,  leukocytes  average,  17,000;  poly- 
morphonuclears, average,  78  per  cent. ;  large  lymphocytes,  average,  6.3  per 
cent.:  small  lymphocytes,  average,  10.1  per  cent.;  eosinophiles,  average, 
2  per  cent.;  albumin,  11  per  cent.;  granular  casts,  4  per  cent.;  hyaline  casts, 
2.5  per  cent.;  blood  cells,  4  per  cent.;  myocarditis,  6  per  cent.;  irregular 
heart,  3  per  cent.;  murmurs,  8  per  cent.;  mastoiditis  (no  facial  palsy  in  this 
series),  1  per  cent.;  arthralgia   (all  cases  had  immunizing  doses  of  diph- 

'From  tl.e  American  Jmnnal  of  llie  Medical   Sciences,  Novcnilier,   1912. 

Page  SS 


RAXSOHOfF  MEMORIAL  VOLUME 


theria  antitoxin),  6  per  cent.;  acetone,  49.5  per  cent.;  diacetic  acid,  22.6 
per  cent. ;  indican,  73  per  cent. ;  temperature  gone  in  five  and  two-third 
days;  nephritis,  2  per  cent.  The  average  white  count  of  cases  which  died 
was  17,262.  Preponderance  of  the  staphylococcus  may  have  influenced  all 
leukocyte  counts. 

Concerning  the  ahove  summary  a  few  comments  seem  pertinent :  (  )nset 
with  vomiting  occurred  in  only  50  j.er  cent,  of  our  cases,  which  is  rather 
disappointing,  as  so  much  stress  has  always  been  laid  upon  this  sign. 
McCullom'  says  tliat  it  occurred  in  80  per  cent,  of  his  cases,  but  Welsh  and 
Schamberg  give  their  figures  also  as  50  per  cent.,  and  add  that  they  con- 
sider this  rather  lower  than  usual.  I  think  that  this  is  a  just  criticism  and 
that  in  most  epidemics  the  figures  would  be  considerably  higher. 

\Ve  observed  mouth  jiallor  in  57  per  cent.,  which  is  also  lower  than  we 
would  expect.  No  statistics  were  olilainable  from  other  sources  in  regard 
to  this,  McCullom  merely  s,iy>  lli.it  it  docurs  constantly  in  moderately  severe 
cases.  It  has  been  our  e.xiJcricnce  that  the  rash  occurs  on  the  face  in  only 
a  small  number  of  the  cases,  but  when  this  is  present  or  if  there  is  only  a 
febrile  blush  upon  the  cheeks,  the  skin  around  the  mouth  and  nose  remains 
exempt.    When  this  is  seen  I  believe  it  to  be  quite  characteristic. 

Thirty-eight  and  six-tenths  per  cent,  had  rashes  upon  the  .soft  palate  and 
fauces  and  where  this  is  present,  namely,  a  generalized  blush,  punctate  in 
character.  I  believe  it  to  be  our  most  important  diagnostic  sign. 

The  papilke  appeared  enlarged  in  56  per  cent,  of  our  cases.  Concerning 
this  McCullom  says  that  the  condition  is  constant,  but  may  be  missed  at 
times,  and  Welch  and  Schamberg  say  that  it  may  or  may  not  be  present  in 
mild  cases.  When  present,  even  with  the  glazed  tongue  (17.7  per  cent.),  it 
is  not  absolutely  pathognomonic,  as  it  may  occur  in  certain  forms  of  gastro- 
intestinal disturbance  in  which  there  is  not  the  slightest  suspicion  of  scarlet 
fever.  The  strawberry  tongue,  however,  taken  together  with  a. generalized 
blush,  punctate  in  character,  upon  the  soft  palate  and  fauces,  need  leave  very 
little  doubt  as  to  the  character  of  the  disease. 

I  think  these  two  symptoms  arc  \ery  nuicli  more  significant  than  an 
apparently  characteristic  rash  upon  the  body.  We  have  tried  to  emphasize 
the  importance  of  laying  more  stress  upon  the  mouth  .symptoms  and  not 
depending  upon  the  body  rash.  However,  the  whole  jjicture  should  be  con- 
sidered 

Our  average  white  count  was  17,000.  The  maxinunn  was  viS.OOO.  The 
text-books  lead  us  to  expect  a  uniformly  higher  count  than  this.  We  felt 
that  a  satisfactory  one  was  between  20,000  and  35,000.  Kotschetkofif  and 
Bowi's"  figures  are  between  10,000  and  40,000,  Reider's  40,000,  Felsenthal 
between  18,000  and  30,000,  and  Tileston  between  18.000  and  40,000. 

The  average  polymorphonuclear  count  was  78  per  cent.  Kotschetkofif 
gives  between  85  and  98  per  cent. 

1.  Osier's  Motlcrn    Mcdirine. 

2.  Qnolcrt   liy    Welch   and    .Scli.im1)C.g. 


ALBERT  J.  BELL 


The  low  percentage  of  eosinophiles,  2  per  cent.,  was  probabl_v  due  to  the 
fact  that  the  blood  counts  were  made  early  in  the  disease. 

McCulIom  observed  albumin  in  72  per  cent,  of  his  cases  at  the  South 
{department,  while  Roger  reports  38  per  cent.  Our  cases  showed  the  pres- 
ence of  albumin  in  only  11  per  cent.  I  believe  that  a  practical  reason  for 
this  may  be  found  in  our  routine  treatment.  All  cases  were  confined  to  bed 
for  at  least  three  weeks  and  kept  upon  a  strictly  milk  diet  until  their  tem- 
]ieratures  were  normal  for  seven  days.  Eggs  and  broths  were  withheld 
until  the  fifth  week  and  red  meats  until  the  latter  part  of  the  sixth.  Of  equal 
importance  with  this  is  the  systematic  giving  of  large  quantities  of  water 
from  the  time  of  their  admission  to  the  hospital.  At  first  potassium  citrate 
was  ordered,  more  or  less  as  a  placebo,  to  be  given  hourly  or  two  hourly  in 
water,  with  the  idea  that  the  patients  would  get  the  fluid  more  religiously 
if  medicine  were  ordered  with  it.  How  much  restraining  influence  the  alka- 
linizing  power  of  this  drug  exerted  upon  the  i)resence  or  absence  of  albumin 
in  the  urine  we  will  consider  later. 

In  our  estimate  of  nephritis  we  included  all  cases  showing  the  presence 
of  albumin,  casts,  and  red  blood  cells,  and  this  we  found  to  be  only  2  per 
cent.  Welch  and  Schamberg''  quote  Vogl  as  reporting  34  per  cent,  of 
nephritis  in  his  cases;  Cadet  de  (lassicourt,  30  ])er  cent.;  Ilaginsky,  9.57  jier 
cent.;  Caiger,  3.32  per  cent.,  and  Holt  gix'es  as  his  figures  between  G  and  10 
per  cent. 

Let  me  call  attention  to  the  fact  that  about  50  per  cent,  showed  the  pres- 
ence of  acetone  in  the  urine;  less  than  half  that  number  showed  diacetic  acid. 
and  almost  75  per  cent,  reacted  for  indican. 

Practically  all  the  cases  desquamated,  although  some  very  slightly. 

None  of  our  scarlet  fever  cases  contracted  diphtheria  in  the  house, 
although  two  or  three  showed  the  presence  of  the  Klebs-Loefiler  bacillus 
upon  admission.  The  most  susceptible  period  for  this  disease  is  the  third, 
fourth  and  fifth  week.  Variat  and  Deve  report  30  cases  positive  for  the 
Klebs-Loeiifler  bacillus  in  525  scarlet  fever  ]iatients ;  Garret  and  Washburn.^ 
London  Fever  Hospital,  report  1  per  cent. ;  \\'elsh  and  Schamberg,-  Munic- 
ipal Hospital  in  Philadelphia  found  between  19  and  32  per  cent,  positive. 
Some  allowance  should  be  made  for  the  method  employed  in  reporting  the 
presence  or  absence  of  the  Klebs-Loeffler.  We  used  the  Westbrook  classifi- 
cation entirely,  which  is  liberal  and  will  be  referred  to  under  diphtheria. 
At  least  four  cultures  were  taken  from  the  noses  and  throats  of  all  scarlet 
fever  patients. 

The  so-called  Pastias  sign  in  this  disease,  namelv,  the  accentuation  of  the 
rash  in  the  normal  folds,  especialh-  on  the  anterior  surface  of  the  elbow. 
has  not  been  noticed  except  in  a  few  instances,  so  that  no  significance  has 
been  attached  to  it. 


RANSOHOFF  MFMORIAL  VOLUME 


Of  like  importance  is  the  Rumpel-Leeds  phenomenon  or  the  hemorrhages 
at  the  elhow  from  compression  of  the  upper  arm  by  means  of  a  bandage. 
Observations  made  by  others  have  shown  it  to  occur  with  equal  frequency 
in  measles  and  in  normal  children. 

In  taking  up  the  treatment  of  special  conditions  we  may  first  refer 
briefly  to  the  subject  of  immunization  against  scarlet  fever.  We  have  had 
practically  no  personal  experience  with  this  line  of  work,  except  to  give  one 
light  case  which  was  exposed  to  the  most  virulent  form  of  the  disease  one 
million  killed  streptococci  taken  from  scarlet  fever  patients  (a  vaccine  which 
was  on  the  market)  and  which  case  continued  to  ha\e  a  mild  attack,  and 
another,  a  very  malignant  case,  five  daily  doses  from  500.000  to  4,000,000 
of  the  same  scarlet  fever  vaccine.  This  patient's  condition  was  uninflu- 
enced by  the  treatment  and  the  patient  died  in  a  few  days.  The  above 
should  come  under  the  heading  of  treatment  of  the  disease  rather  than 
immunization.  If  there  is  any  close  connection  between  the  streptococcus 
and  the  virus  of  scarlet  fever  we  would  look  for  our  best  results  from  an 
antistreptococcus  serum,  made  from  scarlet  fever  patients  rather  than  a 
vaccine,  as  the  former  (the  serum)  already  contains  the  antibodies  and 
should  act  more  promptly,  while  tlie  latter  (the  vaccine)  simply  helps  the 
patients  to  form  his  own.     The  field  for  the  vaccine  is  in  immunization. 

With  the  use  of  the  ordinary  antistreptococcic  serum  made  up  of 
streptococci  not  from  scarlet  fever  patients  we  have  noticed  little  benefit 
even  in  doses  of  80  or  90  cc.  in  twenty-four  or  thirty-six  hours.  If  it  is 
used  at  all  it  should  be  made  from  the  streptococci  from  blood,  throat,  or 
glands  of  scarlet  fever  cases.  Such  a  serum  has  been  hard  for  us  to  obtain 
from  any  source,  because  of  tlie  difticulty  we  have  experienced  in  isolating 
streptococci  from  our  cases. 

Federinski  in  ]VIoscow  (1910).  in  an  analysis  of  317  cases  which  received 
the  antistreptococcic  serum  (made  from  scarlet  fever  streptococci),  says 
that  it  helps  chances  of  recovery  if  given  before  the  fifth  day.  His  dosage 
was  200  cc.  to  adults  and  100  to  150  cc.  to  children,  repeated  in  twenty-four 
or  forty-eight  hours  if  necessary.  Mathias  Nicoll,  New  ^'ork  (1910),  re- 
ports only  fair  results.  If  obtainable,  it  should  be  used  in  some  cases,  in 
enormous  doses  always,  for  lack  of  something  better,  either  subcutaneously 
or  intravenously,  according  to  immediate  needs.  It  might  help  minimize  the 
complications 

Professor  Schwenkenbecker,  director  of  the  Frankfurt  Hospital  Medical 
Clinic,  recommends  the  injection  intravenously,  not  later  than  the  fourth 
day,  of  serum  (healthy  as  to  syphilis  or  tuberculosis  and  culturally  sterile), 
taken  from  at  least  three  (namely,  a  polyvalent  serum)  scarlet  fever  cases 
suffering  from  a  severe  but  uncomplicated  type  of  the  disease  in  late  conval- 
escense.  Treatment  with  this  sera  should  cease  not  later  than  the  eighteenth 
to  the  twenty-fourth  day  from  the  onset.  The  dose  should  be  40  cc.  for 
children  and  100  cc.  for  adults,  and  doses  may  be  given  at  intervals  of  from 


ALBERT  J.  BELL 


one  to  seven  days  according  to  the  severity  of  the  case.  He  suggests  that 
only  the  severe  and  unquestioned  cases  of  scarlet  fever  be  injected. 

Karl  K.  Koessler  and  Jessie  M.  Koessler.'"'  in  experiments  concerning 
specific  antibodies  in  scarlet  fever,  concluded  that  "the  serum  of  scarlet 
fever  patients  contains  specific  antibodies  for  an  unknown  virus  which 
seems  to  be  present  especially  in  the  cervical  lymph  glands."  Personallv,  I 
think  that  we  should  direct  out  eflforts  toward  discovering  a  specific  serum 
for  the  treatment  of  this  disease  to  the  preparation  of  sera  derived  from  the 
blood  stream  or,  more  probably,  from  (lie  cervical  lymph  glands  of  scarlet 
fever  patients,  rather  than  to  vaccines  or  serums  containing  the  streptococcus 
or  its  antibodies. 

Out  of  50  or  more  nurses  who  have  been  on  duty  in  the  wards,  three 
(about  6  per  cent.)  contracled  the  disease  in  the  house,  while  none  of  the 
internes  did. 

W.  H.  Waters,  of  Boston,  reports  results  in  immunization  against  scarlet 
fever,  of  nurses  on  contagious  duty.  He  used  diiiferent  strains  of  strepto- 
cocci, killed  and  standardized  in  usual  way,  taken  from  throats  of  scarlet 
fever  patients.  For  two  or  three  weeks  before  going  on  duty  the  nurses 
received  three  immunizing  doses,  of  50,000,000,  100,000,000  and  200,000,000 
organisms  of  a  polyvalent  vaccine.  Of  those  receiving  the  vaccine  2.7  per 
cent,  contracted  the  disease  and  of  those  not  receiving  it  35.7  per  cent,  con- 
Iracted  it.  These  figures  are  rather  amazing  as  his  nurses  must  have  been 
unusually  susceptible. 

Kolmer  of  Philadelphia,  in  trying  to  raise  the  streptococco-opsonic  index, 
found  experimentally  that  he  was  able  to  do  so  slightly,  but  concluded  that 
it  was  so  slight  as  to  make  the  likelihood  of  establishing  an  immunity  against 
streptococcic  infection  very  dubious.  Again,  in  experimental  studies  on 
streptococcus  antibodies  with  special  reference  to  complement  fixation  reac- 
tions, he  concludes  that  a  streptococcus  produces  a  specific  antibody  up  to  a 
certain  limit,  but  "finding  but  11.2  per  cent,  of  positive  reactions  in  scarlet 
fever  tends  to  show  that  streptococcus  infection  in  scarlet  fever  severe 
enough  to  produce  immune  bodies  is  not  so  common  as  is  generally  believed," 

Nasal  and  ear  discharges  were  reported  promptly  and  a  number  of  auto- 
genous and  stock  vaccines  (in  all  ten,  an  inconclusive  number  it  is  true~)  were 
prepared. 

It  is  the  opinion  of  most  workers  that  stock  vaccines  gi\e  equally  as 
good,  if  not  better  results  than  the  autogenous,  because  the  former  can  be 
administered  much  more  promptly  and  several  days  are  gained  for  the 
patient,  a  very  important  consideration.  Our  results  with  these  vaccines 
were  not  brilliant.  Cases  using  vaccines  had  no  local  treatment.  Irrigations 
were  employed  for  the  others.  Except  in  one  or  two  instances  we  could  not 
see  that  the  discharge  was  in  any  way  modified  by  the  vaccine  and  on  the 
whole,  those  having  local  treatments  ran  a  shorter  course.     The  dosage  in 

6.     Jour.    Infect.   Dis.,   Novcniliev,    1911,   v,.l.    i.x.   No.    3, 

Page  27 


RAXSOHOFF  MFMORIAL  VOLUME 


each  case  was  started  with  ahout  200.000  and  each  succeeding  dose  was 
doubled  at  intervals  of  from  two  to  ten  days,  according  to  indications.  This 
was  carried  up  to  128.000,000  in  some  cases.  Tliis  method  has  so  far  been 
disappointing,  but  in  the  hands  of  Kolmer.  of  Philadeljihia,  good  results 
have  been  reported.  It  is  possible  that  in  some  instances  our  intervals  of 
administration  and  dosage  were  faulty,  yet  the  method  is  certainly  in  line 
with  modern  vacine  therapy  in  other  directions.  Many  cases,  however,  hav- 
ing local  treatments,  where  intelligently  applied,  yield  results,  which,  if 
vaccines  were  being  used,  would  be  considered  brilliant. 

We  have  taken  the  opportunity  in  our  wards  of  applying  where\er  feas- 
ible, the  treatment  for  nephritis  as  suggested  by  Dr.  Martin  Henry  Fischer.' 

This  therap\  is  based  upon  certain  theories,  or  more  correctly,  facts, 
since  they  have  been  confirmed  by  laboratory  experiments  and  as  they  are 
a  departure  from  our  formerly  accepted  views  on  nephritis,  it  may  be  well 
to  briefly  summarize  a  few  details  of  his  work  and  conclusions  for  the  benefit 
of  those  who  are  not  familiar  with  them.    They  are  as  follows : 

It  is  assumed  that  nephritis  is  due  to  an  acidosis  in  the  kidney.  Empha- 
sis is  laid  upon  the  colloidal  structure  of  the  blood,  both  red  and  white  cor- 
puscles and  the  lic|uid  ]X)rtion,  also  that  the  urinary  membrane,  namely, 
everything  between  the  urine  and  the  blood,  consists  of  various  emulsion 
colloids  in  the  solid  state.  Colloid  material  is  also  present  in  the  urine  nor- 
mally, but  is  not  visible  as  albumin  to  our  ordinary  tests. 

The  fluids  and  tissues  of  the  body  (except  the  gastric  juice,  urine,  sweat, 
vaginal  secretion,  and  alimentary  contents,  when  fat  is  fed)  are  practically 
neutral  in  reaction.  Normal  blood  is  neutral  in  reaction,  but  contains  both 
alkalies  and  acids. 

An  abnormal  production  or  accumulation  of  acid  in  the  kidney  renders 
the  colloidal  urinary  memliranc  solul)le  and  permits  a  part  of  it  to  ]iass  into 
the  urine  as  albumin. 

This  has  been  demonstrated  bv  ex])erimcnts.  Fibrin,  an  albuminous 
structure,  when  mixed  and  shaken  with  plain  water  (of  neutral  reaction) 
swells  only  slightly  and  the  water  shows  no  reaction  for  albumin.  If  h)dro- 
chloric  acid  is  added  there  is  greater  swelling  of  the  fibrin  and  albumin  is 
present  (by  the  precipitation  of  the  fibrin)  in  the  water  in  accordance  with 
the  amount  of  swelling.  If  sodium  chloride  or  any  other  salt  is  mixed  with 
the  hydrochloric  acid,  less  albumin  goes  into  solution,  the  higher  the  con- 
centration of  the  salt.  Geletin  (anotlier  colloid)  acts  practically  the  same 
way  as  fibrin. 

A  high  alkali  content  can  as  readily  put  the  colloids,  fibrin,  and  gelatin 
into  solution  (namely,  dissolve  the  albumin)  as  can  an  acid.  This  is  jn-ob- 
ably  no  factor  in  the  production  of  a  nephritis  as  the  normal  (!^J.  ijroduction 
in  the  living  cells  tends  c|uickly  to  neutralize  it. 

Fischer  found  that  liy   injecting  acid  into  the  ear  of  a   ralibit,  its  nor- 

7.     Nephritis. 
Page  2S 


ALBERT  J.  BELL 


mally  alkalin  urine  became  acid.  Albumin,  casts,  epithelial  cells,  blood  cor- 
puscles, and  hemoglobin  appeared  promptly  in  the  urine  which  was  also 
diminishefl  in  cpiantity.     Edema  of  the  tissues  was  noticed  as  well. 

An  over  snppl}'  of  acid  in  the  tissues  in  extreme  muscular  exertion  anrl 
the  se\rrc  ;ineniias,  without  adequate  oxicl.-ilinn.  shnws  alhuniin  in  the  in'ine. 

Contrary  to  the  views  of  many,  he  holds  that  albuminuria  is  the  constant 
accompaniment  of  salt  star\ation. 

Actual  experiments  on  the  kidney  by  Fischer  are  in  line  \\ilh  the  pre- 
ceding observations.  He  found  that  the  structures  of  the  kidne_\-  in  the  pres- 
ence of  an  acid  swell,  take  in  water,  and  part  of  the  colloid  material  is  dis- 
solved as  albumin  and  precipitated  as  granules. 

This  brief  summary  suggests  the  "Fischer"  treatment  for  nephritis, 
namely,  an  alkali,  salt,  and  plenty  of  water. 

It  occurred  to  us  that  as  the  contagious  diseases  are  frequently  accom- 
panied by  an  acidosis,  as  exemplified  by  the  presence  of  acetone  in  about  50 
per  cent,  of  our  cases  and  diacetic  acid  in  22.6  per  cent.,  that  the  alkaline 
treatment  might  help  to  control  the  progress  in  the  severe  septic  types  of 
the  disease.  Apparently  it  exerted  little  or  no  influence  in  staying  the  coiu'se 
of  the  purely  septic  types  which  were  unaccompanied  by  any  special  ni'phri- 
tis.  Fischer  says  that  he  would  not  exjiect  it  to  have  any  material  influence 
upon  that  type  of  case.  Sodium  carbonate  given  by  the  mouth  was  not  well 
tolerated  as  a  rule,  and  seemed  to  be  somewhat  more  irritating  to  the  rectum 
than  a  normal  salt  solution.  However,  a  large  majority  of  the  cases  retained 
a  sufficient  amount  in  that  way.  Potassium  citrate  was  substituted  when 
giving  an  alkali  by  mouth  and  has  been  given  to  all  my  cases  hourly  or  two 
hourly,  whether  or  not  they  had  evidences  of  albumin  or  nephritis.  Prob- 
ably the  low  percentage  of  albuminurias  (11  per  cent.)  and  that  of  nephritis 
(2  per  cent,  in  388  cases  of  scarlet  fever)  observed  in  our  wards  is  due  to 
the  routine  alkaline  "plenty  of  water"  treatment,  which  all  the  cases  have 
had.    Their  urine  part  of  the  time  was  alkaline  and  never  highly  acid. 

Two  cases  present  interesting  features  : 

Case  I. — M.  D.,  male,  aged  three  years.  vSevere  se])tic  type  with  liotli 
ears  discharging,  profuse  nasal  discharge,  enlarged  glands,  weak,  irregular 
heart  with  bruit  at  apex,  eyelids,  and  feet  edematous.  Urinalysis,  albumin 
negative.  Amount  of  urine  \ery  scanty,  blood  cells  and  hyaline  casts.  Started 
alkaline-salt  solution  per  rectum.  The  solution  contained  sodium  carbonate 
(crystals)  10,  sodium  chloride  10,  in  1000  cc.  of  water.  A  half  strength 
dilution  of  the  above  was  used.  Four  ounces  were  given  per  rectum  every 
three  hours  and  were  expelled  occasionally.  Potassium  citrate,  grains  live 
in  water,  was  given  by  mouth  every  one  to  three  hours. 

On  the  ninth  day  of  the  illness  Fischer's  solution  was  gi\en  intraven- 
ously. Same  formula  as  above  was  used  except  that  sodium  cbhn-ide  \\,-is 
increased  to  14  in  the  1000  cc.  of  water  and  a  half  dilution  given.  (  )nl\ 
10  ounces  were  used  as  the  patient  showed  signs  of  collapse.    At  least  a  pint 

Fagc  S'J 


RAXSOHOFF  MEMORIAL  VOLUME 


and  a  half  should  have  been  gi\en  very  slowly  had  we  been  able  to  do  so. 
Next  day  one  pint  was  given  again  intravenously.  The  amount  of  urine 
passed  increased  promptly,  and  the  edema  disappeared.  Gradual  improve- 
ment of  general  symptoms  with  complete  recovery  resulted. 

Case  II. — J.  D..  male,  aged  four  years.  Light  case  of  scarlet  fever  with 
temperature  reaching  normal  on  the  fifth  day.  He  passed  from  8  to  33 
ounces  of  urine  daily  up  to  the  thirty-first  day  of  the  illness.  On  the  twenty- 
seventh  day  (end  of  fourth  week)  the  urinalysis  showed:  Specific  gravity, 
1010;  albumin,  a  heavy  trace;  few  coarse  granular  casts;  red  and  white 
blood  cells. 

The  child  was  somnolent  and  was  aroused  with  dilticulty.  \'omited  sev- 
eral times.  Pulse  varied  between  90  and  122.  with  blood  pressure  high 
(systolic  pressure  sometimes  reaching  144).  The  child  seemed  on  the 
verge  of  uremic  convulsions.  There  was  pufliness  of  the  face  and  eyelids 
and  slight  edema  of  the  feet.  There  was  no  fluid  in  the  serous  cavities  at 
any  stage. 

For  thirteen  days  after  the  nephritis  commenced,  except  once,  albumin 
from  a  slight  to  a  heavy  trace  was  reported  daily  in  twenty-four  hour  speci- 
mens.   It  then  disappeared  not  to  return  again. 

During  the  presence  of  albumin,  red  and  white  cells  were  found  in 
abundance.  Casts  were  rare.  An  occasional  granular,  and  a  few  blood  casts 
were  reported  once  and  part  of  one  cast  another  time.  There  were  no  hyaline 
casts.  After  eight  days  the  blood  cells  were  few  in  number  and  gradually 
disappeared,  to  be  entirely  gone  about  the  eighteenth  day.  The  specific 
gravity  varied  between  1002  and  1028,  usually  between  1002  and  1010.  The 
urine  was  reported  as  acid  only  twice  after  the  fourth  day.  The  amount  of 
urine  passed  daily  varied  from  30  to  60  ounces. 

Treatment.  The  treatment  was  as  follows  :  For  ten  da}s  after  albumin 
was  discovered  the  patient  had  sodium  chloride,  grains  five,  and  potassium 
citrate,  grains  eight,  by  mouth  in  as  much  water  as  he  would  take  every 
hour,  day  and  night.  Fischer's  solution,  one-half  dilution  (of  the  sodium 
chloride  10,  sodium  carbonate,  crystals  10.  water  1000  cc.  strength),  ounces 
five,  per  rectum  was  given  at  two-hour  intervals  during  the  day  and  three- 
hour  intervals  during  night,  and  was  retained.  After  ten  days  the  intervals 
of  administration  both  by  mouth  and  rectum  were  lengthened. 

During  the  period  of  high  blood  pressure,  veratrum  viridi.  minims  two. 
every  three  hours,  was  given  during  the  day.  Fischer's  solution  intraven- 
ously was  not  necessary. 

Blaud's  pills  were  started  during  convalescence  as  a  tonic.  During  the 
attack  the  child  showed  a  mild  grade  of  anemia.  The  red  blood  cells  were 
4,600,000.     Recovery  was  complete. 

There  were  several  interesting  features  about  this  ca>e.  He  started  with 
what  appeared  to  be  a  terrific  case  of  nei)hritis  with  the  urine  absolutely 
loaded  with  red  blood  cells  and  a  large  amount  of  albumin.     One  striking 


Page  30 


ALBERT  J.  BELL 


thing  was  the  great  scarcity  of  casts  of  all  descriptions.  How  much  this 
was  influenced  by  keeping  the  urine  absolutely  alkaline,  by  the  constant 
administration  of  salt,  and  the  ingestion  of  large  quantities  of  water,  is  an 
interesting  question.  With  the  starting  of  the  treatment  all  symptoms 
improved  and  continued  to  do  so  consistently. 

We  found  that  grains  twelve  to  thirteen  hourly  of  potassium  citrate  by 
mouth  in  the  adult  and  grains  five  to  seven  in  children,  aged  four  to  seven 
years,  was  sufficient  to  keep  the  urine  alkaline. 

As  I  have  said  before,  nephritis  has  been  of  rather  rare  occurrence  in 
our  wards,  but  whenever  tried  the  alkaline  salt  treatment  has  given  satisfac- 
tory results. 

True  relapses  or  reinfections  were  not  observed,  but  delayed  rashes 
occurred  in  one  or  two  instances. 

Eighteen  blood  cultures  were  made  during  the  year  from  scarlet  fever 
patients.  Of  these  nine  were  negative.  In  the  other  nine  cases  the  staphy- 
lococcus pyogenes  aureus  was  recovered  seven  times  and  the  albus  twice. 
We  were  unable  to  recover  the  streptococcus  from  the  blood. 

The  throat  and  nose  cultures  almost  uniformly  showed  the  presence  of 
staphylococci,  occasionally  mixed  with  a  few  streptococci. 

Atmospheric  plate  cultures  (88  in  number)  in  wards  before  fumigation 
showed  the  presence  of  the  staphylococcus  aureus  and  albus,  the  strepto- 
coccus pyogenes,  but  never  the  Klebs-Loefifler  bacillus.  After  fumigation 
with  formaldehyde,  plate  cultures  were  always  negative. 

Twelve  cervical  glands  of  scarlet  fever  patients  were  aspirated  with 
aseptic  precautions  in  an  effort  to  corroborate  the  claitns  of  X'ijsond  made 
in  the  spring  of  1911,  that  he  had  found  the  specific  organism  of  scarlet 
fever  in  the  glands  of  patients  suffering  from  this  disease.  The  cultures 
were  sterile  in  nine  cases ;  the  staphylococcus  pyogenes  aureus  was  isolated 
twice  and  the  pyoscyaneus  once.  Our  results  did  not  verify  his  findings. 
This  has  also  been  the  experience  of  others.  Experiments  by  Dr.  Nicoll 
.show  that  Mpond's  bacillus  was  probably  a  contamination  from  the  asbestos 
packing  of  his  syringe. 

The  following  summary  shows  observations  made  u])on  76  cases  of 
diphtheria : 

Onset  with  sore  throat,  84  per  cent.;  onset  with  vomiting,  ii  per  cent.; 
membrane  on  tonsils,  85  per  cent. ;  membrane  on  soft  palate,  36  per  cent. ; 
inflammatory  swelling,  30  per  cent. ;  membrane  gone  on  the  average  in  two 
and  seven-elevenths  days ;  temperature  normal  on  the  average  in  three  and 
three-quarter  days;  erythema  (not  from  serum),  5  per  cent.;  urticaria  (not 
from  serum) ,  14  per  cent. ;  otitis,  5  per  cent. ;  albumin,  12  per  cent. ;  adenitis, 
47  per  cent. ;  paralysis,  soft  palate,  5  per  cent. ;  paralysis  of  other  muscles, 
4  per  cent. ;  myocarditis,  16  per  cent. ;  endocarditis,  28  per  cent. ;  slow  inilse, 
4  per  cent.;  arthralgia,  2.6  per  cent.;  acetone,  28.5  per  cent.;  diacetic  acid, 
14  per  cent.;  indican,  i2  per  cent.;  serum  rashes,   16  per  cent.;  antitoxin, 


RANSOHOFF  MFMORIAL  VOLUME 


average  dose.  4O,C0O  units;  highest  dose,  355.000  units;  l)l()od  count: 
Leukocytes,  average.  13,633. 

Types  of  Klebs-Loeffler  bacilH  found  in  Wesbrook  ckissitication :  C,  58 
per  cent. ;  D.  39  per  cent. ;  A.  22  per  cent. ;  E,  8  per  cent. ;  E.  and  Fo,  5  per 
cent. ;  B,  D,.  and  F,,  3  per  cent.    Other  solid  forms  occurred  less  frequently. 

Glancing  at  the  table  we  see  that  vomiting  occurred  at  the  onset  in  only 
18  ])er  cent,  of  the  cases,  while  in  scarlet  fever  the  percentage  was  50. 

A  striking  feature  about  the  table  is  that  the  average  dose  of  antitoxin 
was  40,000  units.  This  is  accounted  for  by  the  fact  that  a  number  of 
desperate  cases,  having  been  sick  about  a  week  before  admission,  required 
enormous  doses  which  brought  up  the  average  considerably.  Many  re- 
quired only  small  doses.  Our  rule  w^as  to  give  from  2000  or  3000  to  12,000 
units  from  two  to  three  times  in  twenty-four  hours,  until  signs  of  improve- 
ment were  noticed. 

A  husband  and  wife,  sick  one  week  before  admission,  came  in  completely 
overwhelmed  by  the  disease.  The  former  had  the  pharyngeal  type,  his 
pharynx  being  completely  covered  by  a  membrane  about  one-eighth  of  an 
inch  thick.  He  had  the  record  dose,  355,000  units.  He  developed  some 
arrhythmia,  but  showed  no  serum  rashes  or  arthralgia.  He  was  in  an 
advanced  stage  of  tuberculosis  before  acquiring  diphtheria  and  died  from 
that  disease  later.  His  wife  had  a  bad  laryngeal  type  of  diphtheria,  with 
pronounced  stenosis,  loss  of  voice,  and  extreme  prostration.  She  received 
345,000  units  and  made  a  complete  recovery,  without  serum  rashes,  arthral- 
gia, evidences  of  myocarditis,  or  any  other  complication.  .Xdxanced  laryn- 
geal cases  received  antitoxin  unsparingly. 

Whether  or  not  hospital  cases  receive  more  antitoxin  than  is  absolutely 
necessary,  they,  at  least,  cannot  be  judged  by  the  standard  set  in  private 
practice  where  the  cases  receive  treatment  promptly. 

Our  cases  show  some  features  which  are  worth  mentioning.  'I'he  average 
time  for  the  disappearance  of  the  membrane  was  two  and  two-third  days 
and  normal  temperature  averaged  three  and  three-fourth  days.  Paralysis 
of  the  soft  palate  occurred  in  only  5  per  cent.  Other  paralysis,  4  per  cent. 
.Arthralgia  was  noticed  in  only  2.6  per  cent,  and  serum  rashes  in  16  per  cent. 
Concentrated  serum  was  always  used.  No  anaphylactic  phenomena  were 
observed  in  any  of  our  cases.  Our  mortality  for  diphtheria  as  reported  up 
to  January  1,  1912.  was  3j/i  per  cent.,  while  for  scarlet  fever  it  was  6.5  per 
cent.  This  is  at  least  an  illustration  of  the  principle  that  large  doses  of 
antitoxin  need  not  be  feared,  and  that  it  neutralizes  all  the  toxin.  The  con- 
verse applies  forcibly  to  insufficient  dosage.  Promptness  in  administration 
is  an  important  guide  to  the  size  of  the  dose. 

The  Wesbrook'  classilication  was  used  routinely  in  examinaticjns  for 
the  Klebs-Locffler  bacillus.     .A,  C,  and  1).  the  granular  types,  were  regarded 


Public   Hygiene.    May, 


ALBERT  J.  BULL 


as  positive  and  when  found  three  successive  negative  cuhures  were  required 
before  discharge. 

A,,  A,„  B,  Bo,  C,  C..  and  E  (the  barred  types  except  E),  were  called 
doubtful,  and  when  found  put  the  patient  back  for  only  one  culture  instead 
of  three.  The  solid  forms  were  regarded  as  negligible.  This  method  is  a 
liberal  one.  as  it  makes  a  distinction  between  the  virulent  and  non-virulent 
types. 

Xo  use  was  made  of  the  Diazo  reaction  in  di])luheria  as  a  differential 
sign  between  a  purely  serum  rash  and  true  scarlet  (.)r  measles.  It  occurs  in 
17  per  cent,  of  scarlet  fe\er  cases,  12  per  cent,  of  diphtheria,  and  75  per 
cent,  of  measle  cases.     In  the  latter  it  might  be  helpful. 

Little  difficulty  was  experienced  with  the  persistence  of  the  Klebs-Loeffler 
bacillus  in  the  throats  of  convalescing  individuals.  This  happened  only  two 
or  three  times.  The  early  negative  findings  were  undoubtedly  influenced  by 
frequent  throat  irrigations  and  sometimes  nasal,  of  normal  salt  solution  or 
bichloride  solution  (1  to  12,000)  or  simple  applicatons  of  the  latter  (1  to 
4000). 

L.  M.  DeWitt  and  others  recommend  the  application  and  sprays  of 
fresh  cultures  in  broth  of  the  staphylococcus  pyogenes  aureus  for  persistent 
Klebs-Loeffler  bacilli  in  the  throat.  This  should  not  be  done  until  convales- 
ence,  when  the  mucous  membrane  presents  a  normal  healed  surface.  There 
is  no  incompatibility  between  the  Klebs-Loefffer  and  the  staphylococcus,  but 
the  latter  assists  in  reinforcing  the  normal  throat  flora. 

Max  Crohn''  recommends  small  doses  uf  antitoxin  (2000  units)  subcu- 
taneously  for  post-diphtheritic  paralysis  and  reports  good  results.  We  have 
not  tried  it,  and  should  hesitate  to  do  so  except  in  very  favorable  cases  for 
fear  of  serum  sickness. 

BingeP"  recommends  intraspinal  injections  of  diphtheria  antitoxin  for 
late  cardiac  failure  after  this  disease.  The  condition  is  so  grave  that  any- 
thing which  gives  even  remote  promise  should  be  tried. 

Cumberlage,  of  England,  recommended  the  use  of  antitoxin  by  the  mouth. 
The  initial  dose  was  4000  units,  followed  up  if  necessary  by  2000  units 
more.  He  did  not  observe  serum  rashes  or  joint  pains  following  the  use  of 
this  method,  and  obtained  result  within  a  few  hours  after  administration. 

W'e  tried  this  with  a  few  cases  (five  in  number)  and  selected  them  with 
reference  to  mildness  rather  than  severity  of  type.  It  was  administered  in 
milk  and  usually  well  borne.  We  used  only  small  doses,  but  seeing  very 
slow  response  gave  more  than  he  recommended.  The  average  disappear- 
ance of  nasal  discharge  was  five  and  one-half  days  and  of  membrane  on  the 
tonsils  seven  and  one-third  days,  as  opposed  to  the  subcutaneous  method, 
which  was  two  and  two-third  days. 


RAXSOHOFF  MEMORIAL  VOLUME 


\\'ith  the  injection  of  diphtheria  antitoxin  intravenously  we  have  had  no 
experience.  E.  Freedberger  and  S.  Mita"  claim  from  their  experiments  that 
larger  doses  may  be  borne  and  that  there  is  less  chance  of  an  anaphylactic 
reaction  when  applied  directly  to  the  blood  stream  and  so  avoiding  a  reac- 
tion with  the  body  tissues.  In  very  desperate  cases  it  might  appeal  to  us 
as  offering  a  better  chance  to  more  promptly  neutralize  the  toxins. 

Acetone  was  found  in  our  diphtheria  patients  in  only  28.5  per  cent.,  but 
only  one  examination  was  made  for  each  of  the  cases.  F.  Reicher.'=  of 
Hamburg,  found  it  in  65  per  cent,  of  his  diphtheria  patients  during  the 
febrile  stage  and  in  40.2  per  cent,  of  all  other  anginas  and  is.  therefore, 
inclined  to  regard  it  as  of  diagnostic  signiticance.  I  cannot  see  that  it  is 
needed  especially  as  an  aid.  for  either  a  laboratory  or  clinical  case  of 
diphtheria  will  have  its  apjiropriate  treatment.  Even  in  private  practice  one 
should  not  be  satisfied  with  just  one  negative  culture. 

Our  routine  method  of  staining  for  the  Kelbs-Loeffier  bacillus  lias  been 
done  with  the  standard  Loeffler's  methylene  blue.  \'ery  recently  we  have 
tried  in  conjunction  with  this  a  slain  jiroposed  by  Dr.  Marie  Raskin'^  in  a 
paper  read  before  the  Royal  Clinical  Institute,  of  St.  Petersburg.  The  solu- 
tion is  composed  as  follows:  5  cc.  of  glacial  acetic  acid.  95  cc.  of  distilled 
w-ater,  100  cc.  of  95  per  cent,  alcohol,  4  cc.  of  an  old  and  long-standing 
methylene  blue  solution,  4  cc.  of  Ziehl's  carbol  fuschin. 

The  method  is  to  drop  the  mixture  on  the  prepared  slide  and  then  boil 
over  a  flame  for  eight  to  ten  seconds.  After  five  seconds  tlie  slide  i>  washed 
in  water,  dried,  and  examined.  The  polar  bodies  ajjpear  as  deep  blue,  while 
the  rod  is  a  bright  red. 

Practically,  our  stains  so  far  show  the  rods  to  be  a  pinkish  color,  while 
the  granules  stand  out  very  well  as  dark  bodies.  (  )ther  rods  and  cocci  like- 
wise take  the  pink  stain.  From  our  limited  experience  in  its  use,  it  appears 
to  be  a  good  stain  and  I  think  that  the  polar  bodies  stand  out  more  promi- 
nently than  with  the  methylene  blue  method  alone. 

Before  closing  let  me  mention  a  few  observations  concerning  measles  and 
rubella.  Our  average  white  count  for  all  ages  in  both  was  between  7000 
and  8000,  somewhat  higher  than  we  would  expect.  All  had  an  increased 
polymorphonuclear  count. 

The  cervical  and  submaxillary  glands  were  enlarged  in  practically  all 
of  our  rubella  cases,  but  in  none  markedly  so.  The  submetal  gland  was 
enlarged  in  a  few  cases  (recent  cases  show  their  presence  more  often),  the 
post-auricular  were  enlarged  more  frequently.  In  rubella  the  rash  was  of 
the  macido-papular  type  in  81  i)er  cent. :  of  tiie  erythematous  type  in  19  per 
cent. 

In  measles,  acetone  and  diacetic  acid  (each)  were  present  in  22  per  cent 
which  is,  I  believe,  lower  than  usual.     Indican  occurred  in  88  per  cent. 

11.  ncutscli.   med.   Wocli.,   rel)iuaiy.    1912. 

12.  Miinch.  med.  Wocli.,  October,    1911. 

13.  Dentsch.   med.   Woch.,   December,    1911. 


ALBERT  J.  BELL 


In  rubella  both  acetone  and  diacetic  acid  were  negative  in  all  cases,  a  fact 
which  may  be  found  to  have  some  diagnostic  significance ;  indican  was  posi- 
tive in  50  per  cent. 

In  conclusion  I  wish  to  express  my  appreciation  of  the  efficient  work 
done  in  the  laboratory  by  Dr.  William  H.  Peters,  the  bacteriologist,  and  liy 
Mr.  King  and  Mr.  Bader,  of  the  Ohio-Miami  Medical  School,  whose  results 
are  incorporated  in  this  article.  To  Dr.  Samuel  Zielonka  I  am  indebted  for 
several  valuable  translations.  It  would  also  be  unfair  to  close  without  grate- 
ful recognition  of  the  services  of  the  internes  and  nurses  who,  from  time  to 
time,  have  been  on  duty  at  the  hospital,  for  without  their  help  this  paper 
would  have  been  impossible. 


REPORT   OF   XIXETEEN    CASES   OF    HYPERFLASIA    OF   THE 
THYMUS  i;LAND,  TREATED  BY  THI-".  X-RAYS.* 

By  Jri.iEx  E.  ]]enjamin,  M.  D..  and  Sidney  Lange,  M.  D. 

Cincinnati. 

HISTORICAL. 

In  1855  Kajip  called  attention  to  in.stances  of  sudden  death.s  in  child- 
hood following  cyanosis  and  stridor,  in  which  at  autopsy  nothing  abnormal 
except  an  hjperplastic  thymus  could  be  found.  Since  that  time  clinicians 
have  paid  much  attention  to  thymic  hyperplasia  and  faulty  involution 
thereof.  The  studies  of  .-\.  Paltauf  in  1889  established  the  frequent  com- 
bination of  hyperplasia  of  the  thymus  with  status  lymphaticus  and  aplasia 
of  the  cardio-vascular  system.  It  was  he  who  called  attention  to  the  neces- 
sity of  considering  causes  other  than  mechanical  in  the  sudden  deaths  among 
such  ])atients.  He  spoke  of  a  disturliance  connected  with  a  "lymphatico- 
chlorotic  constitution." 

For  a  long  time  it  was  thought  that  an  abnormally  large  thymus  was 
always  accompanied  by  a  status  lymphaticus.  but  it  is  now  delniitely  known 
lliat  a  status  thymicus  can  occur  independently  of  a  status  Ix-mpliaticus. 
This  has  been  proven  from  both  laboratory  and  clinical  standpoints.  For 
instance,  W'eisel  and  Hedinger-  have  shown  that  hyperplasia  of  the 
chromaffin  system  and  status  lym]jhaticus  go  hand  in  hand,  while  in  pure 
hypertro]ihy  of  the  thymus  this  is  not  true. 

The  cases  which  are  recorded  in  this  pajx-r  rejirescnt  a  larger  number  of 
cases  of  true  thymic  hyperplasia  than  have  heretofore  l)ecn  rc]3orted.  In 
no  case  were  there  symptoms  of  status  lymphaticus.  Thymic  hypertrophy 
thus  became  a  distinct  entity  with  as  yet  no  cure. 

In  1896  Rehn  reported  5  cases  of  thymectomy  for  the  relief  of  tracheal 
obstruction.  Shortly  before  this  thymopexy  was  employed,  but  was  ;i  com- 
jiletc  failure,  excej)!  for  temporary  relief  of  stenosis.  Thymectomy  was 
resorted  to  entirely  in  these  cases  until  1903,  the  mortality  associated  with 
this  operation  being  about  11  per  cent.  In  this  year  Heinicke"  showed  that 
X-rays  have  a  profound  influence  on  lymphoid  tissue  in  the  guinea  pig,  espe- 
cially on  the  thymus  gland.  With  this  discovery  a  very  valuable  chapter 
was  added  to  medicine,  for  it  was  not  long  liefore  it  was  shown  that  by  the 
immediate  and  intensive  application  of  X-rays,  the  most  hopeless  case  could 
be  saved ;  also,  that  all  the  symptoms  resulting  from  an  enlarged  thymus 
could  be  permanently  cured  by  subsequent  dosage.  The  first  case  thus 
treated  was  reported  by  Dr.  .\lfred  Friedlander.^  Led  by  the  work  of 
Heinecke,  Dr.  Friedlander  and  Dr.  Sidney  Lange  first  worked  with  guinea 
pigs,  noting  the  efi:'ect  of  frequently  repeated  exposures  on  the  lymphoid 
iLssues.     Not  long  after  this  a  case  of  acute  tracheal  stenosis  on  the  basfs 


'From   A.chive.s  of  Pediatiics,   I-cbni.iry,   1918.     Rend  befoi 
n.ili,   Ohio,   l-\bru:iry,    1917. 


JULIEN  E.  BENJAMIN  AND  SIDNEY  LANGE 


of  thymic  hypertrophy  was  relieved  and  permanently  cured  by  the  applica- 
tion of  the  X-rays.  At  this  early  date  one  difficnlty  existed.  Radiography 
was  far  from  its  present  stage  of  perfection  and  it  was  almost  impossible 
to  obtain  clear  pictures  of  the  thymic  region.  Furthermore,  there  was  no 
real  accurate  method  of  measuring  dosage.  It  is  because  of  the  i>assing  of 
these  diflicullies  that  the  present  report  and  results  are  possible. 

I'his  stud}'  criniprises  one  year's  observation  on  all  kinds  of  cases  coming 
under  our  su]ier\isi(in  at  the  Children's  Department  of  the  University  of 
Cincinnati  ( Uhio-Miami  Medical  College)  Clinic.  A  total  of  225  cases  were 
seen  in  that  time,  of  which  19  showed  undisputed  evidence  of  enlarged 
thymus,  or  8.47  per  cent. 

The  diagnosis  of  an  enlarged  thymus  is  usually  simple.  The  chief  com- 
l)laint  is  nearly  always,  coughs  or  attacks  of  choking  which  come  and  go. 
appearing  frequently  in  paroxysms.  One  point  of  interest  is  the  fact  that 
the  mothers  usually  explain  that  the  child  does  not  show  the  prodromal 
symptoms  of  a  cold,  but  while  apparently  well,  begins  to  cough  during  the 
night.  This  is  repeated  for  several  nights  and  then  disappears,  to  return  in 
a  similar  manner  in  a  very  .short  while.  Only  on  further  cross  examination 
is  the  information  elicited  that  there  is  noted  occasional  cyanosis  or  tend- 
ency to  choke  or  stridor.  Most  of  the  cases  were  very  well  developed  and 
nourished.  The  lymphatic  glands,  other  than  the  posterior  cervical  glands 
showed  no  hypertrophy  as  a  rule.  The  spleen  was  found  enlarged  in  only 
two  cases.    The  lungs  were,  as  a  rule,  peculiarly  free  of  rales. 

In  outlining  the  gland  the  following  method,  spoken  of  by  Sylvester'' 
and  others  as  "Threshold  Method  of  Percussion"  was  always  employed: 
The  child  is  placed  on  the  mother's  lap  on  his  back.  Percussion  is  begun 
well  out  in  the  chest  with  such  light  strokes  that  when  the  ear  is  within  a 
few  inches  of  the  area  under  percussion  only  faintest  possible  resonance 
is  heard.  When  sound  disappears,  dullness  begins.  Some  observers  outline 
the  borders  of  dullness  by  the  tactile  sense  of  resistance  rather  than  soinid. 
'IMie  outer  limits  are  determined  much  more  easily  than  the  lower  boundary. 
The  lower  boundary,  which  may  be  oljtained  by  auscultatory  percussion  is 
relatively  less  important.  The  percussion  outlines,  determined  in  this  way, 
correspond  remarkably  close  to  the  roentgenograms.  All  cases  showing 
enlarged  thymus  by  physical  examination  or  in  which  there  were  suggestive 
symptoms  of  this  condition  were  submitted  for  X-ray  examination.  Treat- 
luents  were  only  given  to  those  showing  positive  X-ray  findings. 

It  is  most  interesting  to  note  the  rapid  impro\-ement  under  roentgeno- 
therapy. Beginning  with  the  first  treatment  marked  [progress  is  usually 
noted.  Shortly  after  the  second  treatment  the  cough  has  usually  abated. 
With  the  improvement  in  symptoms  goes  a  corresponding  shrinkage  in  the 
size  of  the  gland  as  shown  by  subsequent  radiograms. 

The  iiarents  were  always  cautioned  about  relapses  which  occur  in  a  cer- 
tain number  of   cases  and  directed  to  return   for  treatment   regardless  of 

Page  37 


RAXSOHOPF  MEMORIAL  VOLUME 


appearance  of  symptoms  within  six  weeks  of  the  last  treatment.  Three 
treatments  are  the  usual  number  given. 

In  reviewing  the  clinical  literature  of  the  past  five  years  one  is  struck 
by  the  small  number  of  cases  reported  of  this  apparently  common  illness. 
Furthermore  it  will  be  noticed  that  most  of  the  cases  which  do  come  into 
])rint  have  been  of  the  fulminating  type.  It  is  altogether  likely  that  the 
cases  coming  under  this  series  represent  earlier  stages  of  the  more  severe 
kinds.  In  other  words,  were  they  to  have  had  intercurrent  infections  while 
in  the  stage  of  hyperthymetism  more  urgent  symptoms  might  have  been 
noted.  It  is  probable  that  the  condition  was  remedied  before  further  symp- 
toms could  develop.  The  condition  is  important  enough  to  deserve  more 
attention  than  has  been  given  to  it  in  the  past.  Early  diagnosis  and  prompt 
therapy  may  be  the  means  (jf  eliminating  most  of  the  sudden  deaths  among 
infants  and  young  children. 

Dr.  Lange  outlines  his  method  of  treatment  as  follows:  All  of  the  chil 
dren  who  were  referred  to  the  X-ray  laboratory,  were  first  radiogra])hed  to 


Plate  1.    r   G 
of    iidcturnal    cmul 
.Vote  lirnadetiMig   it 


confirm,  if  possible,  the  clinical  diagnosis.  To  obtain  trustworthy  X-ray 
plates  of  these  cases  certain  details  of  techni(|ue  must  be  ob.served.  Un- 
doubtedly the  difficulty  experienced  in  some  laboratories  of  establishing 
definite  X-ray  diagnoses  of  thymus  enlargement  has  been  due  to  a  failure  to 
observe  these  details  of  technique.  Indeed,  in  many  large  clinics  the  great 
frequency  of  enlargement  of  the  thymus  glands  in  young  children  has  been 
overlooked  and  in  some  instances  even  doubted.  While  a  clinical  diagnosis 
of  thymic  enlargement  is  not  always  difficult,  yet  it  is  never  absolutely  posi- 
tive without  X-ray  confirmation.  This  X-ray  confirmation,  taken  in  con- 
junction with  the  startling  results  of  X-ray  therapy,  eniphasizes  this  condi- 

Pagc  3S 


JULIEN  H.  BENJAMIN  AND  SIDNEY  LANGE 

tion  as  a  distinct  clinical  entity  and  leads  to  the  recognition  of  many  cases 
which  would  be  otherwise  overlooked. 

The  child  to  be  radiographed  must  be  placed  flat  upon  the  back.  There 
must  be  no  tilting  to  either  side.  If  there  is  the  slightest  lateral  tilting  there 
is  produced  upon  the  X-ray  plate  an  asymmetry  of  the  two  halves  of  the 
chest  and  a  "flopping"  or  displacement  of  the  mediastinal  and  heart  shadows 
to  one  or  the  other  sides.  X-ray  plates  produced  under  such  conditions  are 
usually  valueless,  as  they  cannot  be  accurately  interpreted.  It  is  not  always 
easy  to  place  very  young  infants  symmetrically  upon  their  backs,  but  repeated 
trials  must  be  made  until  a  plate  is  produced  which  shows  the  chest  areas, 
that  is,  the  distances  from  the  midline  of  the  spine  to  axillary  borders  of  the 
ribs,  to  be  equal  on  the  right  and  left  sides.  Under  these  conditions,  enlarge- 
ments of  the  upper  mediastinal  shadow,  whether  to  the  right  or  to  the  left 
of  the  midline,  can  lie  readily  recognized.  It  is  essential  in  the  making  of 
these  radiographs  of  very  young  children  that  the  exposures  be  almost 
instantaneous.     The  reasons  are  obvious. 


as   Plate   1.     November  7,  1916,  after  tlire 
relief  of  symptonr^. 


In  the  series  here  presented  the  time  of  ex])osure  varied  from  one-sixtieth 
to  one-thirtieth  of  a  second.  Even  with  such  short  exposures  it  is  not  always 
possible  to  secure  absolutely  sharp  contours  upon  the  plates.  If  the  time 
exceeds  one-thirtieth  of  a  second  there  restilts  an  amount  of  blurring  of  the 
shadow  contours  which  usually  renders  the  interpretation  inaccurate.  A 
very  soft  X-ray  tube  should  be  used  on  this  work,  as  the  delicate  thymus 
tissue  will  fail  to  cast  a  shadow  upon  the  X-ray  plate  if  the  quality  of  the 
X-ray  employed  be  too  hard  or  penetrating. 

As  previously  stated,  the  X-ray  diagnosis  of  thymic  enlargement  is 
based  upon  an  enlargement  (usually  a  lateral  enlargement)  of  the  thynuis 
shadow,  which  normally  rests  upon  and  is  continuous  with  the  heart  shadow. 


RAXSOHOFf  MEMORIAL  VOLUME 


Since  the  breadth  of  the  upjier  mediastinal  shadow  \-aries  normally  with  the 
age  and  general  condition  of  the  patient  and  since  it  may  vary  from  time  to 
time  even  in  the  same  patient,  the  X-ray  diagnosis  is  not  always  easy  or  free 
from  error.  In  one  case,  not  included  in  this  series,  an  apparently  normal 
thymus  shadow  was  obtained  when  the  child  was  quiet  or  sleeping,  but 
during  a  restless  crying  spell  the  thymus  shadow  became  greatly  enlarged. 

The  X-ray  shadows  of  congenital  heart  enlargements  are  often  confused 
with  th}'mic  enlargements.  In  all  cases  in  wiiich  the  X-ray  diagnosis  seemed 
doubtful  an  X-ray  exposure  was  given  as  a  therapeutic  test,  and  this  test 
has  proven  very  reliable.  It  must  be  conceded,  in  this  connection,  that 
many  sym])tomless  and  apparently  healthy  children  may  show  an  appar- 
ently enlarged  thymus  upon  the  X-ray  plate  and  this  fact  has  been  illogically 
cited  as  evidence  against  the  accuracy  of  the  X-ray  diagnosis  and  the  value 
of  X-ray  treatment  of  thymic  enlargements.  An  enlarged  thymus  in  an 
apparently  healthy  child  may  be  abnormal  although  its  ill  effects  may  not 
be  manifest  until  some  added  strain  be  ])u(  u[)on  the  heart  or  respiratory 
organs  or  until  the  resisting  powers  of  the  child  be  called  upon  to  overcome 
an  acute  infection.  Post-morten  evidence  is  not  always  conclusive  in  these 
cases  as  a  thymus  enlarged  intra  vitam  may  collapse  after  the  circulation 
is  abolished,  although  such  post-mortem  findings  have  been  cited  as  indicat- 
ing inaccuracy  in  X-ray  interpretation. 

The  X-ray  therapy  was  carried  out  in  this  series  of  cases  as  follows : 
A  Coolidge  tube  backing  up  a  9^/2 -inch  spark  was  employed.  The  rays  were 
filtered  through  four  millimeters  of  aluminum  and  a  piece  of  thick  leather. 
The  target  skin  distance  was  approximately  9  inches.  The  routine  exposure 
was  25  milliampereminutes.  In  mild  cases  a  single  dose  given  over  the 
anterior  surface  of  the  chest  proved  sufiicient.  In  more  urgent  cases  50 
milliampereminutes  were  administered  at  the  first  treatment.  25  anteriorly 
and  25  posteriorly.  During  the  treatment  the  child  was  kept  quiet  by  four 
sandbags,  one  placed  across  each  arm  and  one  across  each  leg.  The  interval 
between  treatments  was  usually  one  week  unless  the  urgency  of  the  symp- 
toms suggested  more  frequent  applications.  The  treatments  have  proxen 
entirely  harmless  to  young  children,  and  if  the  symptoms  are  very  urgent  a 
.second  dose  may  be  given  within  a  day  or  two  after  the  first.  In  order  to 
get  results  it  is  essential  that  the  treatments  be  comparatively  heavy  and 
that  they  be  repeated  at  sufficiently  short  intervals.  The  failure  to  adminis- 
ter full  doses  and  to  repeat  them  promptly  has  in  very  urgent  cases  led  to 
fatalities  under  X-ray  treatment.  Such  a  distressing  occurrence  is  fortu- 
nately uncommon,  but  when  it  does  happen  it  casts  a  doubt  upon  the  diag- 
nosis or  upon  the  efficiency  of  the  X-ray  therapy.  To  guard  against  sud- 
den deaths  before  the  full  destructive  effect  of  the  X-ray  upon  the  thymus 
gland  has  been  elicited,  all  cases  with  urgent  symptoms  should  be  kept  under 
close  observation  and  the  X-ray  treatments  should  be  pushed  boldly. 

Page  Ifi 


J  U  LI  EN  E.  BENJAMIN  AND  SIDNEY  LANGE 

In  the  average  case  improvement  of  symptoms  has  been  noted  within 
24  to  48  hours  after  the  X-ray  treatment.  It  is  possible,  however,  as  shown 
by  animal  experimentation,  to  elicit  changes  in  the  tliymus  gland  within 
eight  hours  after  the  X-ray  exposure.  Therefore  the  most  urgent  cases 
can  be  saved  Ijy  this  treatment. 

COX'CLUSIOXS. 

1.  8.4  per  cent,  of  cases  show  enlarged  thymus. 

2.  Physical  examination.  History  of  symptoms  are  suggestive  of  diag- 
nosis.   X-ray  examination  is  positive  evidence. 

3.  X-ray  treatment  produces  definite  cures. 


HlBLlOr.R 

Paul 

au 

f.    A. 

Wien 

Klin 

W 

ocli.,    1889.    > 

Hedi 

ngcr,   E 

:      Fran 

kfort 

Zei 

5icli,  Path.,  \ 

Miin 

ell. 

Med 

Wocli. 

1903 

p. 

2,090;   1904, 

Arch 

ve 

s  of 

Pediatri 

s:      T 

ilv. 

1907.    p.    490 

liriti 

h 

.\le.l. 

and    Si 

re.    J 

nrr 

.:      \oI.    CL> 

THE    TREATMENT     OF     WOUNDS.     WITH     REFERENCE     TO 
TETANUS  PROPHYLAXIS.* 
Oscar  Berghausen.  P..  A.,  M.D. 

and 

Chari.es  E.  HinvAKn,  M.  D. 

Receiving  Pli\  sician  at  the  Cincinnati  Hospital. 

Cincinnati. 

In  June,  1910,  the  late  Dr.  N.  P.  Dandridge  proposed  the  systematic 
handling  of  all  wounds,  punctured,  penetrating  or  lacerated,  with  the  aim  of 
ascertaining  the  best  methods  of  treating  such  cases  at  a  large  general  hos- 
pital, particularly  with  reference  to  tetanus  prophylaxis.  As  is  well  known, 
to  avoid  the  development  of  tetanus  we  must  begin  by  treating,  in  a  thorough 
surgical  manner,  the  wound  received.  The  use  of  antitetanic  serum  as  a 
prophylactic  agent  was  resorted  to  in  a  large  series  of  cases,  in  order  to 
test  its  value. 

The  following  list  of  instruction.s  were  placed  in  eacli  surgical  ward : 

The  interns  will  please  carry  out  the  instructions  mentioned  below  for  the  follow- 
ing classes  of  cases : 

1.  All  perforating,  penetrating  or  lacerating  wounds  contaminated  directly  hy  soil 
or  manure,  especially  those  contracted  in  the  streets  or  about  stables. 

2.  All  blank-cartridge  and  giant-cracker  perforating  and  lacerating  wounds. 

INSTRUCTIONS. 

1.  In  all  cases  above  mentioned  remove  the  clothing  and  foreign  material  about 
the  wound. 

2.  Cleanse  the  surrounding  parts  with  green  soap,  alcohol,  ether  and  sterile  water. 
.■?.     Remove   with    sterile    forceps   any    foreign    material    lying    superlicially   in   the 

wound. 

4.  Cleanse  the  wound  with  S  per  cent  phenol  (carbolic  acid) -0.5  per  cent  hydro- 
chloric acid  solution. 

5.  Enlarge  the  opening  by  free  incision  if  necessary  to  thoroughly  cleanse  the 
wound,  or  for  the  removal  of  foreign  substance. 

6.  Use  a  general  anesthetic  whenever  indicated. 

7.  Pack  the  wound  lightly  with  gauze  soaked  in  the  phenol-hydrochloric  acid  solu- 
tion, and  dress.     Change  the  dressings  daily. 

8.  Immediately  after  dressing  the  wound  on  the  first  day  give  1.500  units  of  anti- 
tetanic  serum  subcutaneously.     This  serum  can  be  obtained  at  the  laboratory. 

9.  A  careful  record  must  be  kept  and  sent  to  the  laboratory  when  the  patient  is 
discharged. 

10.  In  the  case  of  doubt  or  on  the  appearance  of  symptoms  resembling  tetanu.-.. 
notify  me  [Berghausen]  at  once.  , 

Heretofore  such  injuries  were  opened,  cleaned  and  treated  with  strong 
phenol  solution.  The  object  of  using  the  hydrochloric-phenol  mixture  as 
recommended  in  the  text-books  was  to  test  its  efficiency,  since  it  is  attended 
by  less  necrosis  of  tissue.  Experience  has  shown  us  that  treatment  of  all 
wounds  after  the  above  fashion  was  sufficient.  Particular  care  was  taken  to 
clean  out  all  wounds  thoroughly,  opening  by  incision  if  necessary,  to  remove 
all  foreign  material.  Particularly  is  this  necessary  in  blank-cartridge  wounds 
when  wads  may  have  entered.  In  such  cases,  in  two  instances,  wads  were 
removed  on  successive  days  by  dififerent  interns,  each  one  thinking  that  he 


OSCAR  BERG HAU SEN  AND  CHARLES  E.  HOWARD 

had  removed  the  last  wad.     In  these  cases  a  general  anesthetic  may  become 
necessary. 

To  ascertain  how  many  wads  were  present  in  each  blank  cartridge,  four 
different  s|ieciniens  were  bought  and  examined.  In  each  one  two  wads 
were  found,  but  these  were  found  to  be  rather  loosely  made  and  could  easily 
be  torn  into  fragments. 

AXTITETAXIC  SERUM  AS  A  PROPHYLACTIC  MEASURE. 

Owning  to  the  experience  of  others,  we  have  used  only  one  injection  of 

1,500  units,  usually  given  in  that  part  of  the  anatomy  nearest  the  wound. 

\\'e  repeated  the  injection  in  three  cases  in  which  suppuration  persisted.     In 

this  connection  we  wish  to  quote  the  results  of  Sir  D.  Semple,^  who  says : 

Many  people  in  apparently  good  health  harbar  spores  of  tetanus  in  healed  wounds 
or  in  the  intestinal  tract,  and  that  hidden  away  in  the  tissues  the  spores  remain  alive 
and  retain  their  virulence,  but  do  not  grow  into  toxin-producing  bacilli.  .  .  .  The 
leukocytes  do  not  always  destroy  the  spores,  but  when  a  local  suppuration  has  ceased 
they  may  be  able  to  wander  away  with  the  spores  still  in  them.  .  .  .  Spore-carriers 
are  in  danger  of  suffering  from  tetanus  (a)  on  the  occurrence  of  great  fatigue  or 
exposure  to  heat  or  cold,  which  diminish  their  resistance;  (b)  when  the  site  where  the 
spores  are  lodged  becomes  converted  into  a  medium,  which  from  being  anaerobic  and 
from  a  failure  of  phagocytosis,  is  favorable  for  the  growth  of  the  spores  into  toxin- 
producing  bacilli:  and  (c)  when  a  focus  of  dead  tissue  forms  in  a  part  of  the  body  at 
a  distance  from  the  site  where  the  spores  are  lodged. 

Quinin  given  hypodermatically  may  produce  a  local  tissue  necrosis ;  solu- 
ble non-irritating  substances  do  not.  Scmple  further  ,i>^erts  that  from  10  to 
15  cc.  of  antitetanic  serum  renders  a  patient  pa^si\•c■lv  immune  for  a  period 
of  from  two  to  three  weeks,  and  has  found  it  a  valuable  prophylactic  agent 
when  using  quinin  hypodermatically. 

TABLE  1.    CASES  IX  WHICH  SERUM  WAS  USED  PKOPHVLACTICALLV ; 
GOOD  RESULTS. 

Total  Xo.  Serum  Used, 

Character  of  Injury,                                                          of  Cases  in  Units 

Punctured  wounds  (inostly  made  by  nails) 71  15(X) 

Contused  and  lacerated 4  1500 

Cannon-cracker  wounds    2  1500 

C.un-shot  wounds    6  1500 

Blank-cartridge   wounds    7  1500 

Powder  burns    5  1500 

96 
SERUM  UEACTIOXS. 
These  were  noted  in  several  cases  and  were  marked  by  local  redness, 
swelling,  urticaria-like  eruptions  and  fever.  Owing  to  patients  not  reporting 
as  directed,  we  were  unable  to  obtain  complete  statistics  in  this  regard.  With 
the  aim  of  preventing  such  symptoms  or  of  ameliorating  them  when  once 
developed,  atropin  sulphate  (gr.  1/100-1/120  three  times  a  day,  in  children 
less)  was  given  hypodermatically,  particularly  when  numerous  injections  of 
serum  were  made  in  cases  of  developed  tetanus.  We  have  found  that  this 
drug  possesses  undoubted  value  in  preventing  such  symptoms.  Itching,  red- 
ness   and    urticarial    eruptions    frequently    disappeared    when    atropin    was 

1.  Semple,  Sir  D. :  The  Relation  of  Tetanus  to  the  Hypodermic  or  Intramuscular  Injection 
of  Quinin.    PaUidism.    Simla.  January,   1911.     No,    2,  p.   32. 

Pmje  1,3 


RANSOMOFF  MEMORIAL  VOLUME 


given.  \\'e  therefore  adopted  this  measure  as  a  routine  before  all  repeated 
injections  of  serum.  At  times  such  eruptions  will  appear  following  the  use 
of  ati-opin  sulphate,  but  never  to  a  very  marked  degree. 

In  Table  1  will  he  found  a  list  of  cases  of  patients  treated  at  the  hos])ital 
with  the  aim  of  preventing  tetanus  after  the  method  descrilx-d  in  the  fore- 
going. 

Not  one  case  of  tetanus  developed  in  the  above  series  of  patients. 

In  Table  2  will  be  found  those  ca.ses  in  which  serum  was  not  used  as  a 
|)rophylactic  measure,  and  in  which  the  local  treatment  of  the  wound  was 
good.     Of  this  list  not  one  developed  tetanus. 

TABLE  2.     CASES  IN  WHICH  SERUM  WAS  NOT  USED  PROPHV- 
LACTICALLY:  GOOD  RESULTS. 
Character  of  Injury  No.  Cases         Result 

Punctured  wound — nail   ?>  ( lOod 

Blank-cartridge    ?>  Cmod 

6 
In  Table  3  will  be  found  those  cases  in  which  serum  was  not  used  as  a 
]irophylactic  measure,  and  which  later  developed  tetanus. 

These  patients  were  first  seen  by  us  after  tetanus  had  developed,  except- 
ing cases  1  and  6.  Case  7  occurred  in  the  private  practice  of  Dr.  George 
Krieger.  of  Madisonville,  by  whom  we  were  consulted  and  to  whom  we  are 
indebted.  Case  5  occurred  in  the  service  of  Dr.  Casper  Hegner  at  the  City 
Hospital. 

Two  cases  in  which  serum  was  used  prophylactically,  the  one  caused  by 
a  cannon-cracker  wound  of  the  neck  and  followed  by  extreme  cellulitis 
before  admission ;  the  other,  caused  by  stepping  on  a  nail  and  followed  by 
cellulitis  before  admission,  resulted  in  sudden  death.  No  autopsy  could  be 
secured,  but  death  was  evidently  due  to  an  enibcilus,  no  symi)toms  of  tetanus 
de\elo]iing  and  no  anaphylactic  phenomena. 

RESULTS  WITH  AND  WITHOUT  PROPHYLACTIC  SERU.M  TREATMENT. 

In  the  ninety-six  cases  properly  treated  locally  and  by  the  prophylactic 
administration  of  antitetanic  serum,  not  one  patient  developed  tetanus. 

In  the  fourteen  cases  (Tables  2  and  3)  treated  without  the  i)rophylactic 
administration  of  antitetanic  serum,  eight  patients  developed  tetanus,  of 
whom  six  died. 

In  the  cases  (only  six,  however)  ])roperly  treated  locally  and  without  the 
pro])h\  lactic  administration  of  antitetanic  serum,  not  one  ]>atient  develo])ed 
tetanus. 

Patient  6  ( Table  3 )  was  thoroughly  treated  locally,  but  did  not  receive 
the  prophylactic  serum  injection  and  succumbed  to  tetanus. 

We  had  the  oi>i)ortunity  of  assisting  in  the  treatment  <if  eight  patients 
with  (levelo])ed  tetanus  during  the  past  fifteen  months,  and  feel  that  the 
information  gained  is  of  some  value.  The  usual  methods  of  treatment  were 
employed,  antitetanic  serum  and  phenol  subcutaneous  injections  (  2  per  cent. ) 
included.     Briefly  stated,  our  observations  are  as  follows: 

Page  I,', 


OSCAR  BERGHAUSliX  AXD  CHARLES  E.  HOWARD 

Although  the  cases  with  a  short  incubation  period  offer  the  least  hope, 
such  cases  are  not  necessarily  fatal.  Case  7  was  seen  by  Dr.  Krieger.  the 
first  physician  consulted  in  the  case,  two  days  after  symptoms  of  tetanus 
had  developed,  and  yet  the  manifest  symptoms  disappeared  after  one  week's 
careful  treatment. 

If  antitetanic  serum  is  to  be  used  at  all,  large  doses  must  lie  cm|)loycd. 
although  enormous  doses,  as  reconunended  by  those  interested  in  its  sale, 
were  not  used  by  us. 

Atropin  sulphate  has  some  value  in  controlling  serum  reactions  and  is 
deserving  of  further  trial. 

TABLE   3.     CASES   IN    WHICH    SERUM    WAS    NOT    USED    PROPHYLAC- 
TICALLY  AND  TETANUS  DEVELOPED. 


Cases     Character  nf  bijiir 


1  Multiple  puncture  wound 

made  by  shot 7  —  0  0  —      14  hours Death. 

2  Lacerated  wound 4  —  20,fKH)  0.24  +         .S   davs Death. 

.3     Punctured  wound  (nail)  5  —  0  0.14  +       30  hours Death. 

4  Punctured  wound   ( pick- 

ax)       8  —  .3,000  0  --        4   davs Death. 

5  Cut  hv  a  barl)ed  wire...  14  —  50,000  0  —      14  days Recovery. 

6  Crushed  foot   10  +  27,000  0  —        2  davs Death. 

7  Cut  by  a  scythe 8  0  27.000  0  —  About  2  wks.  Recovery. 

8  Compound   fracture ;   in- 

fected     6  —  27,000  0  ?         2  days Death. 


means   "present."  —   "absent"   and  0   "doubtful." 

The  subcutaneous  administration  of  phenol.  2  per  cent,  solution,  is  fol- 
lowed by  an  early  appearance  of  albumin  in  the  urine.  This  possibility  of 
damaging  the  kidneys  must  be  taken  into  consideration  when  the  injections 
are  used.  In  the  future  we  shall  follow  such  injections  by  the  rectal  admin- 
istration of  a  hypertonic  neutral  -alt  solution  to  limit,  if  possible,  this  dam- 
age to  the  kidneys,  in  accordance  with  the  results  obtained  in  experimental 
nephritis,  by  Prof.  Martin  H.  Fischer,  of  this  city. 

We  feel,  after  a  careful  study  of  such  injuries  as  listed  in  the  foregoing. 
that  no  wound  of  such  a  nature  should  be  treated  lightly  by  any  ])hysician. 
By  carefully  cleansing  each  wound,  using  a  general  anesthetic  if  necessary 
to  remove  all  foreign  material,  and  employing  a  diluted  antiseptic  to  prevent 
sepsis,  and  then  treating  each  one  as  an  open  wound,  the  physican  has  done 
much  to  prevent  tetanus.  By  employing  one  immunizing  dose  of  1500  units 
of  antitetanic  serum,  to  be  repeated  only  when  suppuration  has  not  ceased 
after  a  week,  he  can  jiractically  assure  the  I'atient  perfect  safety  from 
tetanus. 


THE  EARLY  RECOGNITION  OF  HYDROCEPHALUS  IN 

MENINGITIS.* 

Kf.nneth  D.  Bi.ackfan. 

Baltimore. 

Interference  with  absorption  of  the  cerebrospinal  fluid  in  acute  menin- 
gitis may  be  brought  about  by  an  exudate  so  localized  that  it  obstructs  the 
foramen  of  Magendie  and  the  foramina  of  Luschka,  or  the  exudate  may 
block,  partially  or  completely,  the  cisternae  (magna,  interpeduncularis  and 
pontis)  at  the  base  of  the  brain  and  so  prevent  the  free  distribution  of  cere- 
brospinal fluid  throughout  the  cerebal  subarachnoid  space.  The  spinal  sub- 
arachnoid space  may  be  filled  partially  or  completely  with  exudate,  thus 
limiting  the  participation  of  this  surface  in  the  absorption  of  the  cerebro- 
spinal fluid.  \'arious  combinations  of  these  processes  may  coexist.  In  any 
event,  if  the  absorption  of  cerebrospinal  fluid  is  diminished  for  a  sufficient 
length  of  time,  hydrocephalus  is  produced. 

A  brief  discussion  of  the  formation  and  the  circulation  of  the  cerebro- 
spinal fluid  and  the  more  recent  information  concerning  hydrocephalus  will 
not  be  out  of  place  here. 

Cerebrospinal  fluid  is  formed  within  the  ventricles  from  the  activity  of 
the  choroid  plexus.  L'nder  normal  conditions  it  passes  from  the  ventricles 
through  the  various  foramina  (foramen  of  Magendie  and  foramina  of 
Luschka)  to  the  subarachnoid  system  where  it  is  absorbed.  Absorption  in 
the  ventricular  system  is  negligible.  From  the  subarachnoid  system  the  cere- 
brospinal fluid  is  absorbed  directly  into  the  blood  stream.  Although  absorp- 
tion takes  place  from  both  the  cerebral  and  the  spinal  subarachnoid  sys- 
tems, cerebral  absorption  is  much  greater  than  spinal  absorption.  This  is 
due  to  the  fact  that  the  cerebrum  offers  a  much  greater  absorbing  surface 
and  that  a  more  extensive  blood  vascular  area  is  exposed  to  contact  with 
the  cerebrospinal  fluid.  Disproportion  between  the  formation  and  the 
absorption  of  cerebrospinal  fluid  results  in  its  accumulation  and  its  reten- 
tion within  the  ventricles. 

Hydrocephalus  is  secondary  to  some  process  that  interferes  with  the 
normal  circulation  or  absorption  of  cerebrospinal  fluid.  Anatomically,  two 
types  have  been  demonstrated:  (a)  obstructive,  and  (b)  communicating. 
Obstructive  hydrocephalus  develops  because  the  cerebrospinal  fluid  cannot 
pass  from  its  i)lace  of  origin  in  the  ventricles  to  the  cerebral  and  spinal  sub- 
arachnoid space  where  absorption  takes  place.  Communicating  hydroce- 
phalus— the  channels  of  communication  betw-een  the  ventricles  and  the  spinal 
subarachnoid  space  being  patent  to  a  greater  or  less  degree — results  because 
the  cerebrospinal  fluid  cannot  reach  the  cerebral  subarachnoid  space  where 
the  greater  part  of  absorption  takes  place.    In  the  majority  of  instances  this 


•From    the    Harr 
Johns  Hopkins  Unive. 
ber.    1919. 

iet   Lane   Home 
rsily,  Baltiih6re. 

..   John. 
From 

i   Hopkins 
the  Ame 

Hospital 

.    and   the    Department    of   I 
rnal  of   Diseases  of  Childrei 

PagciG 

KEXNETU  1).  BLACK  FAN 


is  due  to  adhesions  which  obHterate  the  various  cisternae  or  centers  from 
which  the  cerebrospinal  fluid  is  distributed  over  the  cortex  of  the  brain.  A 
combination  of  the  two  types  may  result  if,  in  addition  to  interference  with 
the  absorption  of  the  cerebros]Dinal  fluid  from  the  subarachnoid  space,  there 
is  an  inadequate  communication  between  the  ventricular  and  the  subarach- 
noid system. 

The  primary  cause  of  chronic  hydrocephalus  in  a  series  of  cases  studied 
recently  was  a  previous  meningitis  in  fourteen  cases,  a  congenital  absence 
of  the  aqueduct  of  Sylvius  in  three  cases  and  a  tumor  blocking  the  iter  in 
one  case. 

A  differentiation  between  the  two  types  of  hydrocephalus  by  clinical 
signs  alone  is  difficult,  as  the  symptoms  produced  are  essentially  alike.  The 
type  of  hydrocephalus  may  be  suggested  by  the  amount  of  cerebrospinal 
fluid  that  is  obtained  by  lumbar  puncture.  Increase  in  amount  of  cerebro- 
spinal fluid  in  acute  infection  of  the  meninges,  the  influence  of  posture  on 
the  amount  of  fluid  obtained  and  alteration  in  the  pressure  in  the  cerebro- 
spinal system  have  to  be  taken  into  consideration  before  drawing  conclu- 
sions from  the  results  of  lumbar  puncture  alone.  The  two  types  of  hydro- 
cephalus can  be  differentiated,  however,  by  the  phenolsulphonephthalein  test. 
When  phenolsulphonephthalein  is  injected  into  the  ventricle  in  obstructive 
hydrocephalus,  the  dye  does  not  appear  in  the  cerebrospinal  fluid  obtained 
from  the  lumbar  subarachnoid  space  within  forty  minutes,  if  at  all.  Tn 
patients  who  do  not  have  hydrocephalus  and  in  those  with  the  communicat- 
ing type  of  hydrocephalus,  the  phenolsulphonephthalein  appears  promptly 
(in  from  six  to  twelve  minutes).  When  phenolsulphonephthalein  is  injected 
into  the  lumbar  subarachnoid  space  in  communicating  hydrocephalus,  absorp- 
tion of  the  dye  is  greatly  lessened.  Less  than  20  per  cent,  is  excreted  in  the 
urine  within  two  hours,  as  compared  to  35  or  60  per  cent,  in  normal  persons. 
In  obstructive  hydrocephalus,  when  the  cisternae  and  the  meninges  are  not 
affected,  absorption  is  as  prompt  as  in  normal  individuals.  The  phenolsul- 
phonephthalein test  has  been  employed  in  the  study  of  a  comparatively  large 
number  of  patients  with  chronic  hydrocephalus,  and  when  carried  out 
properly  it  affords  accurate  information  regarding  the  patency  of  the  fora- 
mina between  the  ventricles  and  the  subarachnoid  system  and  the  amount 
of  absorption  from  the  subarachnoid  space.  Recently  Dandy'  suggested 
that  cerebrospinal  fluid  removed  from  the  ventricle  by  ventricular  puncture 
be  replaced  by  air.  When  this  is  done  and  a  roentgenogram  is  made,  the 
ventricles  appear  clearly  outlined.  By  this  procedure  a  hydrocephalus  can 
be  demonstrated  and  its  extent  measured. 

It  has  long  been  known  that  hydrocephalus  is  a  frequent  complication  of 
meningitis,  but  until  recently  there  has  been  no  means  by  which  its  early 
recognition  has  been  possible  or  a  differentiation  between  the  two  types  of 

1.  Dandy,  VV.  H.:  .\;ni.  Surg.  68:509  (Dec.)  19IS.  .Ms.,:  .\iu.  1.  RuciilKfU. .!..>;>■  i.:-'o  (Ian. I 
1919;  Bull.  Johns  Hopkins  Hosp.   30:29   (Feb.)    1919. 


RAXSOHOFF  MEMORIAL  VOLUME 


livdrocephalus  could  be  made,  both  of  wliich  are  essential  for  successful 
treatment 

In  the  present  study  I  have  carried  out  the  phenolsulphonephthalein 
test-  in  patients  with  meningitis  in  which  hydrocephalus  has  developed,  and 
I  have  had  roentgenograms  made  after  the  injection  of  the  ventricles  with 
air.''  Particular  attention  has  been  paid  to  the  early  diagnosis  of  hydro- 
cephalus and  to  the  pathologic  findings.  Twenty-five  cases  of  hydrocephalus 
were  studied. 

Meningitis  due  to  the  streptococcus,  the  Stal'hylococcus  aureus,  the  influ- 
enza bacillus  and  the  pneumococcus  is  a  terminal  manifestation  in  the 
majority  of  instances,  secondary  to  a  primary  focus  elsewhere.  The  entire 
course  of  the  meningitis  is  usually  of  short  duration,  w-hich  explains  the 
infrequency  of  hydrocephalus  in  meningitis  due  to  these  organisms.  Hydro- 
cephalus was  observed,  however,  in  the  course  of  a  meningitis  due  to  the 
influenza  bacillus  in  two  patients,  four  and  eight  months  of  age,  respec- 
tively. They  lived  about  two  weeks.  A  communicating  hydrocephalus  was 
demonstrated  at  necropsy  in  one  patient,  and  an  obstructive  hydrocephalus 
in  the  other.  In  the  latter,  the  hydrocephalus  was  suspected,  as  it  was 
impossible  to  obtain  more  than  a  few  drops  of  cerebrospinal  fluid  by  lumbar 
puncture.  The  phenolsulphonephthalein  test  showed  that  an  obstruction 
existed  between  the  ventricular  and  the  subarachnoid  systems,  and  at 
necropsy  the  basal  foramina  were  found  to  be  obstructed  by  a  thick  purulent 
exudate 

The  infre(|uency  of  hydrocephalus  in  tuberculous  meningitis  is  due, 
probably,  to  the  relatively  slight  involvement  of  the  meninges.  It  is  only 
occasionally  that  the  exudate  is  so  situated  or  sufliciently  large  in  amount 
to  interfere  with  the  avenues  of  exit  of  the  cerebrospinal  fluid  from  the 
ventricles  or  to  diminish  the  absorption  from  the  subarachnoid  space  by 
involving  the  cisternae  at  the  base  of  the  brain.  In  tuberculous  meningitis 
two  cases  of  communicating  hydrocephalus  were  demonstrated.  In  each 
patient  phenolsulphonephthalein  appeared  promptly  in  the  lumbar  sub- 
arachnoid space  after  its  introduction  into  the  lateral  ventricle,  but  absorp- 
tion from  the  subarachnoid  space  was  greatly  diminished.  At  the  necropsy 
the  basal  foramina  were  found  to  be  patent,  but  absorption  was  limited  to 
the  spinal  subarachnoid  space  by  an  exudate  involving  the  cisternae.  In  four 
cases  the  hydrocephalus  was  of  the  obstructive  tyi)e.  In  these  patients, 
phenolsulphonephthalein  did  not  appear  in  the  lumbar  subarachnoid  space 
after  its  injection  into  the  ventricles.  The  foramina  of  exit  at  the  base  of 
the  brain  were  obliterated  by  a  tuberculous  exudate  in  these  cases. 

The  majority  of  the  cases  of  hydrocephalus  occurred  in  meningococcus 
meningitis.  Of  twenty-five  cases  occurring  in  the  course  of  acute  meningitis, 
seventeen  were  due  to  the  meningococcus.     Communicating  hydrocephalus 

2.  Dandv.  W.  E..  and  Bl.-irkf.nn.  K.  D. :  t  .\m.  I)i*.  Child.  8:-10(.  (.\,.v.)  19U;  U:.|.'4  (Dec.) 
1917. 

3.  T  wish  lo  rxprcss  my  Ihniiks  to  Hi.  Walter  Dandv  and  to  the  staff  of  the  Uepartment  of 
RorntEenology  for  thfir  assistance  in   makint;  the  roentgenograms. 

Page  .'iS 


KENNETH  D.  BLACKFAN 


developed  in  eight  of  the  seventeen  cases,  and  in  nine  the  obstructive  form 
was  found.  'Pen  of  the  seventeen  patients  in  this  series  died  and  seven 
recovered,  'i'wo  of  the  seven  patients  had  an  obstructive  hydrocephakis  and 
improvement  followed  pr(.)mptly  after  the  introduction  of  antimeningo- 
coccus  serum  into  the  ventricles.  In  four  cases  in  which  a  communicating 
hydrocephalus  was  present,  the  process  became  arrested  after  treatment. 
The  patients  made  an  imeventful  recovery.  One  patient  developed  a  chronic 
hydrocephalus  (communicating).  He  was  three  months  old  and  was  first 
seen  twenty-four  hours  after  the  onset  of  the  meningeal  symptoms.  Men- 
ingococci were  grown  from  the  blood  and  the  cerebrospinal  fluid.  Anri- 
nieningococcus  serum  was  administered  intravenously  and  into  the  lumbar 
subarachnoid  space.  After  the  first  few  days  the  meningococci  disappeared 
for  ;i  time  from  the  cerebrospinal  fluid.  The  temperature  remained  irregu- 
lar. The  meningeal  symptoms  did  not  disappear,  and  from  time  to  time,  in 
s|)ite  of  treatment,  the  organisms  would  reappear  in  the  cerebrospinal  fluid, 
lie  was  treated  intensively  with  serum  introduced  into  the  ventricles  and  the 
hunljar  subarachnoid  space  o\er  a  jieriod  of  twenty-four  days  before  the 
meningococci  disajipeared  permanently  and  the  cerebrospinal  fluid  became 
normal.  Seven  months  after  the  onset  of  the  meningitis,  the  head  was 
greatly  enlarged  and  a  ventriculogram  showed  almost  complete  destruction 
of  the  cortex  (Fig.  1).    The  patient  is  alive  at  the  present  writing. 

A  necrop.sy  was  performed  in  the  ten  fatal  cases,  and  the  clinical  diag- 
nosis was  confirmed  by  demonstration  of  the  exciting  cause  of  the  hydro- 
cephalus. In  seven  cases  (obstructive  hydrocephalus)  an  exudate  occluded 
the  foramina  at  the  base  of  the  brain,  and  in  three  cases  (communicating 
hydrocephalus )  the  basal  cistemae  were  totally  obliterated  by  a  thick  puru- 
lent exudate.  Whether  an  exudate  or  adhesions  are  found  at  necropsy  in 
this  form  of  meningitis  depends  primarily  on  the  duration  of  the  disease. 

It  is  not  within  the  province  of  this  paper  to  discuss  the  pathologic  pro- 
cess met  with  in  the  various  types  of  meningitis.  Acute  hydrocephalus  in 
meningitis  develops  because,  as  in  chronic  hydrocephalus,  there  is  a  diminu- 
tion in  the  absorption  of  the  cerebrospinal  fluid.  The  important  point  to 
recognize  is  that  the  lesion  must  be  so  located  as  to  obstruct  the  outflow  of 
cerebrospinal  fluid  from  the  ventricles  to  the  subarachnoid  space,  or  else 
to  limit  the  area  of  absorption  from  the  spinal  or  cerebral  subarachnoid 
system.  The  disappearance  of  the  exudate  and  the  formation  of  adhesions 
determine  the  transition  from  an  acute  to  a  chronic  hydrocephalus,  and  the 
re-establishment  of  an  ec[uilibrium  between  the  formation  of  cerebrospinal 
fluid  and  its  absorption  determines  whether  the  process  will  become  arrested 
or  advance  progressively.  The  chronicity  of  meningococcus  meningitis 
makes  it  the  form  of  meningitis  ]iar  excellence  for  the  development  of  a 
chronic  hydrocephalus.  Meningitis  due  to  other  organisms  almost  without 
exception  is  fatal,  and  in  a  short  time. 

Page  .}.■) 


RAXSOHOFF  MEMORIAL  VOLUME 


Fig.  1.  Roentgenogram  taken  seven  months  after  the  onset  of  an  acute  attack  of 
meningococcus  meningitis.  The  phenolsulphonephthalein  test  showed  that  there  was 
a  free  communication  between  the  ventricles  and  the  spinal  subarachnoid  space.  Ab- 
sorption from  the  subarachnoid  space  was  9  per  cent,  in  two  hours.  After  air  injection 
the  roentgenogram  showed  the  lateral  ventricles  to  be  markedly  dilated  (A)  and  an 
extreme  grade  of  atrophy  of  the  cortex  (C). 


TABLE  1.     ACUTE  HYDROCEPHALUS  IN  MENINGITIS. 

Type  of  Meningitis 

No.  of  Cases  of 

Meningitis  with 

Hydrocephalus 

Studied 

2 

17 

Type  of  Hydrocephalus 

Obstructive 

Communicating 

9 

a 

Total 

25 

]] 

Attention  may  be  directed  to  a  hydrocephalus  developing  in  meningitis 
by  the  onset  of  certain  symptoms.  The  diagnosis  is  readily  established 
when  the  condition  is  of  long  duration  and  the  symptoms  of  increased  intra- 
cranial pressure — headache,  stupor,  vomiting,  enlargement  of  the  head  and 
changes  in  the  eye  grounds — are  present.  The  early  manifestations  of 
hydrocephalus,  however,  are  so  closely  interwoven  with  the  symptoms  of 
the  meningitis  itself,  that  they  are  often  difficult  to  recognize.  Hydro- 
cephalus should  always  be  suspected  with  the  persistence  of  symptoms  of 
meningeal  irritation  (fever,  hyperesthesia,  irritability  or  drowsiness,  rigid- 
ity of  the  muscles  of  the  neck  and  extremities,  hyperactive  reflexes,  tremors, 
etc.)  or  their  reappearance  after  the  symptoms  of  meningitis  have  subsided. 
Infants  invariably  have  a  tense  and  bulging  fontanel  and  in  children.  Mac- 

Pagc  SO 


KEVNETH  D.  BLACKFAN 


ewen's  sign  is  positive.  It  should  be  remembered  that  these  symptoms  can- 
not always  be  referred  to  the  hydrocephalus  alone.  We  often  see  at  the 
onset  of  acute  meningitis  and  throughout  the  course  of  the  disease  manifes- 
tations indicative  of  increased  intracranial  pressure — headache,  fever,  vom- 
iting and  muscular  rii^'idity-  which  do  not  mean  necessarily  that  hydro- 
cephalus is  present.  I  believe  that  much  confusion  has  been  caused  by  refer- 
ring to  such  a  condition  as  hydrocephalus.  For  instance,  in  tuberculous 
meningitis  there  is  present  quite  constantly  a  marked  increase  in  the  amount 
of  cerebrospinal  fluid,  but  at  necropsy  a  picture  quite  the  reverse  of  that  seen 
in  hydrocephalus  is  found.  The  sulci  are  distended  with  fluid,  the  brain  is 
edematous,  and  though  there  is  a  varying  increase  in  the  size  of  the  ven- 
tricles, one  does  not  find  flattening  of  the  convolutions,  atrophy  and  com- 
pression of  the  brain  substance  and  the  marked  dilatation  of  the  ventricles 
which  characterize  the  latter  condition.  A  number  of  patients  with  tuber- 
culous and  meningococcus  meningitis  who  presented  such  symptoms  have 
been  studied  by  determining  the  amount  of  cerebrospinal  fluid  withdrawn, 
by  the  phenolsulphonephthalein  test  and  the  pathologic  findings  at  necropsy. 
In  these  patients  there  was  no  interference  with  the  absorption  of  cere- 
brospinal fluid  and  at  necro])sy  the  findings  characteristic  of  hydrocei)halus 
were  not  present.  It  is  not  at  all  likely  that  an  increase  in  the  amount  of 
cerebrospinal  fluid  can  produce  other  than  a  temporary  and  insignificant 
hydrocephalus,  unless  there  is  an  associated  diminution  in  the  absorption  of 
the  fluid.     The  results  are  shown  in  Table  2. 

Abnormal  changes  in  the  eye  grounds  and  enlargement  of  the  head,  when 
present,  are  symptoms  indicative  of  an  hydrocephalus,  but  they  are  seldom 
seen  early  in  its  development  and  so  are  of  but  little  aid  in  making  the 
diagnosis.     This  is  especially  true  before  the  fontanels  are  closed  and  the 

T.\BLE  2.    FINDINGS  IN  CASES  OF  MENINGITIS  WITH  INCREASED 
INTRACRANIAL  PRESSURE,  BUT  NO  HYDROCEPHALUS. 


Phenolsaiphonepthalcin 

Spinal 

Fluid 

CaFe 

Diagnosis 

Absorption 
from    Sub- 
arachnoid, 
per  cent. 

Patency   of 
Comnnmi- 

Pressure 

.^mount 
C.c. 

Necropsy 

Tuberculous 

45 

10 

Increased 

40 

Ventricles  not  dilated.  Exu- 
date slight,  not  involving  the 

Tuberculous 

4(1 

12 

Increased 

55 

Ventricles    not    dilated.       Exu- 

meningitis 

date  slight,  not  involving  the 
basal     foramina     or    risternae. 

Tuberculous 
meningitis 

J8 

' 

Increased 

35 

Ventrn  I.-  ..-<  A.'.uA  Exu- 
dal.     -•     ■  ■                  ■.    Uing  the 

Tuberculous 
meningitis 

42 

" 

Increased 

45 

Vcnliu:.  1,  ■  .::  /..I  Exu- 
datf  -l.L-:l,  .  ,.'  r:^..lv,nc  tlie 
basal     fnramn,,,     ..,     M-.,,n,,r 

Meningococcus 

55 

12 

Increased 

dO 

V^entricles    not    .i,-.,i..l        l-n 

meningitis 

date    slight,    HM,     ,:,^,,l,n:,     ,li, 

basal    foraniin. ,.ir,„,„' 

" 

Meningococcus 

48 

in 

Increased 

40 

Ventri.-I.-  ."1  .'■■  ',.1  Ivvn- 
dat,.  ^Im.l.  ,:,,,  ,.  ,,,'>„,g  the 
bas;.l    t,                         .  i^u-rnae. 

meningitis 

45 

Venln.  ;.  i  :  i  ...,l  Exu- 
basal    foramina    or    cisternae. 

RANSOHOFf  MEMORIAL  J'OLUME 


sutures  are  firmly  united.  A  considerable  atroiih)-  and  compression  of  the 
brain  takes  place  before  the  intraventricular  pressure  becomes  sufficient  to 
cause  marked  changes  in  the  eye  grounds  and  an  enlargement  of  the  head. 
This  is  well  illustrated  in  the  case  of  an  infant,  three  months  of  age.  who  was 
observed  from  the  onset  of  an  acute  meningococcus  meningitis  throughout 
the  various  stages  of  development  from  an  acute  to  a  chronic  hydrocephalus. 
This  is  graphically  shown  in  Table  3. 

Table  3.    FINDIXGS  IX  A  CASE  OF  ACUTE  MEXIXGOCOCCUS  MEXIXGITI.S 
DEVELOPIXG  FROM  AX  ACUTE  TO  A  CHROXIC  HYDROCEPHALUS. 


duration 

of 

ference 

Disease 

of    Head 

Com-     (from  Si.h- 

munica-     arachnoid 

tion      '      Space 


Collapse,  fever,  de- 
pressed fontanel, 
petechiae. 

liulpinK  fontanel, 
rigidity,      hyperes- 


Slight  dilatation  Ventricles 

>f  retinal  vessels,  dilated.      Afarked 

Margin  of  disk  I  cortical 

clear.  |  atrophy.  , 

Normal  physi- 
ologic cupping. 

Same  Same 


Ventricles 

greatly 
enlarged. 


Bulging  fontanels, 
separation  of  su- 
tures, craniotabes, 
rigidity,   vomiting, 


The  amount  of  cerebrospinal  fluid  obtained  by  lumbar  puncture  afTords 
the  most  helpful  clinical  sign  of  hydrocephalus,  although,  as  previously 
mentioned,  it  is  not  absolutely  dependable.  In  hydrocephalus  the  cerebro- 
spinal fluid  is  under  greatly  increased  pressure  and  an  abnormal  amount  is 
obtained  readily  or  it  is  obtained  in  small  amount  and  with  difficulty. 

A  definite  increase  in  the  amount  of  cerebrospinal  fluid  of  50  cc.  or  more, 
withdrawn  repeatedly  when  the  other  signs  of  the  acute  infection  of  the 
meninges  have  subsided,  is  significant  of  a  communicating  hydrocephalus. 
While  this  is  suggestive  evidence,  it  is  not  sufficient  in  itself  to  establish  the 
diagnosis,  as  relatively  large  amounts  of  cerebrospinal  fluid  are  sometimes 
found  in  obstructive  hydrocephalus. 

Small  amounts  of  cerebrospinal  fluid  obtained  by  lumbar  puncture  sug- 
gest an  obstructive  hydrocephalus.  If  the  subarachnoid  space  has  been 
entered,  and  the  fluid  is  not  too  thick  to  run  through  the  needle,  it  is  rela- 
tively safe  to  conclude  that  there  is  an  exudate  so  situated  as  to  prevent  the 
free  flow  of  cerebrospinal  fluid  from  the  ventricles  to  the  spinal  subarachnoid 
space.     In  obstructive  hydrocephalus  relatively  large  amount   of   cerebro- 

Pagc 52 


KENNETH  D.  BEACKFAN 


spinal  fluid  may  be  recovered  at  tlie  first  lumbar  puncture  and  then  the 
quantity  lessens  so  that  only  a  few  drops  are  obtained  at  successive  punc- 
tures  (Fig.  2).     Corroborative  evidence  of  the  presence  of  hydrocephalus 


Fig.  2.  Obstructive  lijdroceplialus  in  a  patient  aged  three  months.  The  onset 
of  the  hydrocephakis  was  suggested  ))>■  the  persistence  of  the  s5mptoms  of  meningitis. 
The  cerebrospinal  fluid  was  obtamed  reaUiK  for  ten  da>s  and  then  only  a  few  drops 
flowed  from  the  needle.  The  plun.  ilsiil|ih.>n(  plilh.iKni  test  slicwi-d  that  tlit-re  was  no 
communication  between  the  \cntn.  1.^  .mil  ili,  miK.it. u  hn.  iid  -.p. hi.-.  ,\1is.  niuion  from 
the  subarachnoid  space  was  55  pci  n_iu  m  tu.i  horns  \iur  .ui  mjcction  tlu'  roentgen- 
ogram  showed   dilated  lateral   \(.ntiKli,    (   \\    with    ,ili..pln    <.l    Uie  cortex    (Cj. 

may  be  shown  by  the  results  from  puncture  of  the  ventricle,  as  in  such  cases 
the  cerebrospinal  fluid  in  the  ventricles  is  under  increased  pressure  and  an 
excessive  amount  can  be  withdrawn. 

'i'he  early  recognition  of  hydrocephalus  is  of  practical  importance  in 
meningitis  due  to  the  ineningococcus.  Many  cases  of  hydrocephalus,  the 
result  of  meningococcus  meningitis,  are  reported  in  the  literature  in  which 
the  hydrocephalus  developed  despite  treatment  with  antimeningococcus 
serum.  In  the  majority  of  instances  this  has  occurred  when  treatment  was 
instituted  late,  for  the  outcome  at  this  stage  of  the  disease,  even  with  appro- 

Pmje  M 


RANSOnOfl-  MEMORIAL  I'OLUMR 


in-iale  treatment  is  uncertain  (Fig.  3).  The  earlier  and  tlie  more  intensive 
the  treatment,  the  better  the  chance  of  recovery.  In  obstructive  hydro- 
cephahis  if  the  serum  is  introduced  only  by  lumbar  subarachnoid  injection 
there  is  the  danger  of  organization  of  the  exudate  and  also  that  the  meningo- 
cocci remaining  in  the  ventricles  are  not  subjected  to  the  influence  of  the 
serum.  In  this  form  of  hvdroceiihalus  the  antimeningococcus  serum  should 
l)e  inJL-clud  dircctlv  into  ihe  ventricle  as  well  as  into  the  lumbar  subarachnoid 


(lildttd  \entlicks 
li.ttitiit  ditd  in  s]ii 
lIl-s  ami   intd  tilt- 


,1  patiiiit.  twii  years  old,  wlio  was  un- 
Mi  .i|  an  a.  utc  meningococcus  meningitis. 
P  i-.iii\,  Kruno's  sign  and  a  low  grade  optic 
1  -li  v\(.l  ilial  there  was  a  free  communica- 
hiMid  -.iiaii',  .Misorption  from  the  subarach- 
\ttcr  air  injection  the  roentgenogram  showed 
umpression  of  the  cerebral  cortex  (C).  The 
of  antimeningococcus  serum  into  the  ventri- 


space.  In  communicating  hydrocephalus  intraventricular  injection  of  serum 
also  is  advisable.  A  larger  amount  inay  be  injected -imd  thereby  brought  into 
direct  contact  with  the  exudate  and  in  greater  conceiUration  than  by  the 
lumbar  subarachnoid  injection  alone.     (Fig.  4.) 

The  capacity  of  the  meninges  to  absorb  cerebrospinal  fluid  should  be 
tested  by  the  lumbar  subarachnoid  injection  of  phenolsulphonephthalein, 
when  the  symptoms  of  meningeal  irritation  persist  or  when  they  reappear 
after  the  vigorous  use  of  antimeningococcus  serum.  A  distinct  diminution 
in  the  absorption  of  cerebrospinal  fluid  indicates  a  comnuinicating  hydro- 

Pagc  r,l, 


KENNETH  D.  BLACKFAN 


cephalus.  This  diagnosis  can  be  confirmed  by  determining  the  patency  of 
the  foramina  between  the  ventricular  and  the  subarachnoid  systems  by  the 
injection  of  phenolsulphonephthalein  directly  into  the  ventricle.  If  the 
symptoms  are  the  result  of  an  obstructive  hydrocephalus  the  absorption  of 
the   cerebrospinal   fluid    from   the   luniljar   subarachnoid   space    will    not   be 


Fig.  4.  The  patient,  aged  three  v.ii--,  w.i 
ingocdccus  .serum.  He  did  not  ini|ii.iM  .md 
spinal  fluid.  The  plienolsulphonephth.iK  m  dsi 
arachnoid  space  was  diminished  (1,?  pc  i  nut  i 
the  dye  througli  a  trephine  opening  cliiimnsti . 
tricles  and  the  himbar  subarachnoid  space, 
shows  enlarged  lateral  ventricles  (.AX  the  tre[: 
atrophy  of  the  eerebralcorte.x  (C).  .Xfter  thre 
into    the    ventricles,    the    organisms    disappear 


.\fter  air  injection  the  roentgenogram 
hine  opening  (B)  and  compression  and 
■  injections  of  antimeningococcus  serum 
-d.      The    patient    made    an    uneventful 


diminished.  The  diagnosis  in  this  type  of  hydrocephalus  will  then  (lei)end 
on  the  nonappearance  of  phenolsulphonephthalein  in  the  lumbar  subarach- 
noid space  after  its  injection  into  the  ventricle.  These  tests  add  nothing  to 
the  severity  of  the  treatment.  They  do  not  demand  any  unnecessary  opera- 
tive procedure,  as  under  such  circumstances  it  is  necessary  to  bring  serum, 
either  through  an  open  fontanel  or  through  a  trephine  oi)ening,  in  so  large 
an  amount  and  in  as  concentrated  a  form  as  possible,  directly  in  contact  with 
the  purulent  exudate  at  the  base  of  the  brain. 


STANDARDS  OF  SUCCESS  IX  .MEDICINE.* 
George  Emerson   Brewer. 

In  accepting  the  invitalioii  of  our  President  to  be  present  at  the  annual 
opening  exercises  of  the  medical  school  and  say  a  few  words  to  the  enter- 
ing class,  I  was  somewhat  at  a  loss  to  determine  what  subject  I  should 
choose  which  might  be  of  interest.  I  take  it,  that  in  an  address  of  this  kind 
an  effort  should  be  made  to  suggest  some  thoughts  which  will  be  helpful  to 
the  entering  student  in  arranging  his  time  and  studies  or  informulating 
plans  for  his  future  work,  and  in  addition  to  remind  him  of  the  responsi- 
bilities which  he  is  to  assume,  the  difficulties  he  will  encounter,  and  the  kind 
of  success  he  may  hope  to  attain. 

-As  I  look  about  me  and  study  for  a  moment  the  new  and  unfamiliar 
faces,  differing  as  they  do  in  many  respects  and  conveying  to  my  mind  dif- 
ferences in  character,  temperament,  jjrevious  training,  and  the  ability  to 
work.  I  feel  that  they  express  one  thing  in  common,  namely,  a  determination 
to  begin  in  earnest  the  real  business  of  life.  In  the  preparatory  schools  and 
colleges  your  intellectual  burdens  have  been  lightened  by  a  judicious  admix- 
ture of  recreation,  sport,  and  mutual  companionship;  you  have  enjoyed  long 
periods  of  vacation,  and  at  no  time  have  been  driven  under  high  pressure 
toward  the  attainment  of  a  single  object,  upon  which  will  depend  the  meas- 
ure of  your  success  in  life.  Here  in  the  medical  school  all  will  be  changed: 
you  will  find  conditions  materially  altered,  you  will  be  surrounded  by  an 
atmosphere  surcharged  with  enthusiasm  and  active  competition.  Soon  you 
will  realize  that  to  win  a  prize  or  even  to  receive  an  honorable  mention  in 
the  jirofessional  race  with  your  colleagues,  you  must  at  least  secure  at  the 
end  of  your  college  course  a  creditable  hospital  appointment.  To  obtain 
this  you  must  early  acquire  and  persistently  maintain  a  high  rank  in  your 
class,  and  this  means  hard,  enduring,  concentrated  work,  not  a  few  hours 
each  day,  but  from  ten  to  twelve  or  fourteen  hours  out  of  each  twenty-four 
of  the  college  year,  and  the  willingness  to  devote  at  least  one-third  to  one- 
half  of  your  summer  vacations  to  clinical  work  in  the  various  hospitals  and 
dispensaries  of  the  city.  If  these  conditions  seem  too  severe,  better  matric- 
ulate at  once  in  some  other  medical  school,  for  here  at  the  College  of  Physi- 
cians and  Surgeons  our  standards  are  high,  our  student  body  far  above  the 
average  in  intelligence  and  training,  and  the  pace  set  by  the  leaders  of  each 
class  exceedingly  difificult  to  maintain,  but  we  firmly  belie\e  that  the  rewards 
open  to  the  successful  student  are  well  worth  the  effort. 

This  thought  suggests  the  inquiry  why  so  many  young  men,  well  equipped 
for  almost  any  professional  or  business  career,  choose  annually  to  cast  their 
lot  with  the  medical  fraternity.  It  is  certainly  not  with  any  hope  of  amass- 
ing a  fortune,  for  if  you  do  not  already  know  it.  it  is  only  fair  for  me  to 


'.Address  delivered  .-il  tlie  npenine  exercises  at  the  Collece  of  Plivsici.ins  .ind  Surgeons,  Sei)t 
ber  24.   1913.     I-roiii  The  Cohimbia  University  Quarterly.   .Mar..    191-1. 

Page  SO 


GEORGE  EMERSON  BREWER 


assure  yon  that  the  practice  of  medicine  offers  little  or  no  hope  of  great 
financial  return. 

What,  then  are  the  rewards  of  a  life  devoted  to  tlie  study  and  practice 
of  medicine?  \Miat  are  the  reasons  why  you  have  elected  to  devote  your 
lives  to  a  profession  which  oft'ers  so  little  of  pecuniary  reward  even  to  the 
most  successful  of  its  followers?  I  take  it  that  the  reason  why  so  many 
capable  young  men  enter  our  profession  is  that  they  hope  for  and  expect 
a  reward  which  cannot  be  reckoned  in  dollars  and  cents,  but  which  will  out- 
weigh in  real  value  the  benefits  to  be  derived  from  the  accumulation  e\-en  of 
great  wealth. 

This  brings  me  to  the  announced  subject  of  my  informal  talk  with  you 
this  morning:  What  are  the  standards  of  success  open  to  the  practitioner  or 
student  of  medicine?  Time  will  permit  me  to  mention  only  a  few,  and 
these  I  can  best  illustrate  by  examples.  Take  in  the  first  place  the  practi- 
tioner of  internal  medicine,  the  man  whose  relationship  to  his  patient  is  that 
of  the  family  physician.  Those  of  you  who  are  familiar  with  the  charming 
essays  and  character  sketches  of  Maclaren,  will  recognize  as  one  of  the  best 
of  this  type,  the  rugged  resourceful  old  Scotch  physician,  William  MacLure, 
a  doctor  of  the  old  school,  wlio  preferred  to  practice  his  profession  in  the 
highland  glen  of  his  birth  to  accepting  an  honorable  position  in  one  of  the 
great  medical  centers.  For  forty  years,  day  and  night,  summer  and  winter, 
in  sunshine  and  storm,  through  snow,  ice,  drifts  and  floods,  he  visited  the 
sick  and  injured  of  his  own  village  and  the  scattered  dwellers  of  the  glen. 
It  is  true,  MacLure  was  but  a  character  of  fiction,  created  as  a  composite 
type  from  the  lives  and  virtues  of  hundreds  of  his  class  in  all  parts  of  the 
civilized  world — the  type  of  man  who  gives. all  that  he  possesses  in  kindli- 
ness, sympathy,  and  helpful  assistance  for  a  lifetime,  and  receives  in  return 
only  sufficient  coin  of  the  realm  to  keep  a  roof,  over  his  head,  food  and 
clothing  for  his  body,  but  such  a  harvest  of  esteem,  appreciation,  gratitude 
and  affection,  as  to  fill  to  overflowing  every  desire  of  his  generous  heart. 

Let  us,  however,  turn  from  the  hard  conditions  of  life  of  our  rugged 
Highland  practitioner,  to  the  softer  paths  of  one  of  his  more  fortunate 
lirotliers.  I  have  in  mind  the  career  of  one  of  the  greatest  consultants  and 
teachers  of  medicine  of  our  times.  Reared  amid  scholarly  surroundings, 
graduating  in  medicine  at  an  early  age,  he  quickly  rose  to  a  commanding 
l)osition  in  the  medical  world.  The  master  word  of  his  early  training 
seemed  to  be  work :  constant,  conscientious,  concentrated,  and  systematic 
work.  By  this  means  he  early  acquired  an  enormous  fund  of  medical  knowl- 
edge, and  in  addition  so  trained  his  mind  to  accurate  observation,  accurate 
deduction,  and  accurate  speech,  as  to  fit  himself  admirably  for  the  role  of 
teacher,  in  which  he  later  became  so  successful.  To  watch  him  on  his  hos- 
pital visits  was  a  liberal  education  ;  the  carefully  elicited  history,  the  accurate 
and  painstaking  physical  examination,  the  judicious  employment  of  labora- 
tory aids,  and  finally  the  logical  summing  up  of  the  evidence,  his  masterly 

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RANSOHOfF  MEMORIAL  rOLUME 


analysis  of  the  symptoms  and  signs  of  the  disease  leading  to  the  establish- 
ment of  an  accurate  diagnosis,  as  well  as  his  safe  and  sane  suggestion  in 
regard  to  treatment,  made  him  one  of  the  great  clinicians  of  his  time.  The 
sterling  qualities  of  his  mind,  his  great  industry,  his  charming  personality, 
his  magnetic  enthusiasm  and  withal  his  keen  sense  of  humor,  would  have 
made  him  a  conspicuous  success  in  any  walk  of  life  or  field  of  human  en- 
deavor. In  medicine  few  if  any  practitioners  ever  reached  the  measure  of 
professional  success  which  he  achieved ;  and  no  teacher  ever  inspired  in  his 
students  more  lofty  ideals,  more  enthusiastic  devotion  to  work,  or  more 
loyal  affection  for  their  chief.  William  Osier  never  prized,  sought  after, 
or  accumulated  wealth.  He  always  preferred  an  autopsy  to  a  consultation, 
and  almost  invariably  would  refuse  an  out-of-town  summons  from  a  wealthy 
client  if  it  interfered  with  his  hospital  rounds  or  a  morning  with  the  stu- 
dents. In  his  mental  and  moral  make-up,  there  was  never  any  suggestion 
of  commercialism,  yet  his  professional  success  was  so  great  as  completely 
to  overshadow  any  thought  of  financial  reward. 

It  is  perhaps  the  general  surgeon  whom  the  world  looks  upon  as  reaping 
the  highest  financial  rewards  in  the  medical  profession,  and  yet  one  seldom 
hears  of  a  surgeon  who.se  period  of  large  returns  lasts  more  than  a  few  years. 
Of  all  the  surgeons  of  my  acquaintance,  the  one  whose  life  .semed  to  himself 
and  his  associates  most  rounded  and  filled  with  professional  satisfaction  and 
success,  was  a  man  born  amid  the  humblest  of  surroundings  in  a  small  New 
England  hamlet.  With  educational  opportunities  of  the  most  limited  char- 
acter, by  extraordinary  industry,  undaunted  courage,  and  an  unlimited  capac- 
ity for  work,  he  raised  himself  to  one  of  the  foremost  position  in  surgery  of 
his  time.  Cast  in  a  heroic  moHld.  with  fine  constitution  and  superb  health, 
he  began  his  practice  in  a  western  city,  and  learned  his  surgery  by  hard  per- 
sonal experience.  Receiving  his  degree  long  before  the  antiseptic  era.  he, 
in  common  with  all  others  practicing  surgery  at  that  time,  soon  became 
familiar  with  the  almost  universal  septic  disasters  which  followed  surgical 
operations,  and  yet  by  keen  judgment  and  by  an  almost  superhuman  surgical 
intuition,  he  seemed  to  avoid  in  a  remarkable  degree  the  fatalities  which  fol- 
lowed the  work  of  others.  His  success  inspired  wide  confidence,  and  as  a 
result  of  his  sterling  integrity,  kindly  manner  and  great-hearted  sympathy, 
the  members  of  the  community  in  which  he  lived,  almost  without  exception, 
turned  to  him  in  their  surgical  emergencies.  No  operation  offering  a  rea- 
sonable ho]ie  of  success  was  too  difficult  for  him  to  undertake;  no  sacrifice 
was  too  great  for  him  to  assume,  if  it  contributed  to  the  well-being  or  com- 
fort of  his  patient ;  and  no  man  or  woman  was  too  poor  to  insure  his  best 
efTorts.  His  talents  were  soon  recognized,  and  while  still  a  young  man  he 
was  appointed  professor  of  surgery  in  a  flourishing  medical  school.  His 
reputation  grew  rapidly,  his  skill  was  constantly  in  demand,  by  the  rich  and 
poor  alike,  not  only  of  his  own  city,  but  throughout  the  greater  part  of  his 
own  and  neighboring  states.     His  contributions  to  abdominal  surgery,  then 


GEORGE  EMERSON  BREWER 


in  its  infancy,  his  improvements  in  operative  technic,  and  his  ingenuity  in 
devising  new  and  improved  methods  of  operating  and  wound  treatment 
gave  him  a  national  reputation.  I  never  knew  a  man  whose  life  was  so  full 
of  anxious  work ;  his  expenditure  of  energy  would  quickly  have  disabled  a 
man  of  less  vigorous  constitution.  Although  he  enjoyed  for  his  day  a  large 
income  from  his  wealthy  patients,  more  than  half  his  time  and  efifort  was 
devoted  to  the  less  fortunate  members  of  society,  from^-^'hom  he  received 
little  or  no  compensation.  One  day  in  the  height  of  his  professional  success, 
he  was  called  upon  by  a  physician  of  his  acquaintance  who  asked  him  if  he 
would  operate  upon  a  man  with  strangulated  hernia.  He  explained  (hat 
it  was  impossible  on  account  of  a  college  lecture  and  an  afternoon  filled  with 
appointments  and  urgent  consultations.  His  colleague  replied  that  it  was 
unfortunate  for  the  jjatient,  who  refused  to  go  to  a  hospital  or  allow  any 
one  else  to  o]ierate.  The  surgeon  hesitated,  then  inquired  if  the  man  had 
money.  "No,"  was  the  reply,  "only  an  invalid  wife  and  a  large  family  of 
children."  "Then  I  will  go,"  was  the  reply ;  "poor  devil,  if  he  had  money 
he  could  get  some  one  else."  Quickly  canceling  his  engagements,  he  gath- 
ered his  assistants,  went  to  the  poor  man's  home,  and  performed  a  successful 
operation.  In  performing  the  operation,  successful  for  the  patient,  the 
operator  accidentally  pricked  his  finger  with  a  needle.  That  needle-prick 
ended  the  career  of  this  talented  great-hearted  surgeon — not  by  a  (|uickly 
fatal  infection  with  moderate  suffering,  but  by  a  long-drawn-out,  discour- 
aging and  progressively  weakening  malady ;  for  the  virus  entering  the  veins 
by  this  insignificant  needle  prick  was  the  venom  of  syphilis.  Occurring  at  a 
time  when  the  disease  was  little  understood,  and  treated  with  less  success 
than  at  present,  with  the  kindly  assistance  of  his  professional  colleagues  he 
battled  with  the  virulent  infection  for  weeks,  months  and  years,  only  to 
develop  at  the  end  the  gravest  type  of  cerebral  disease.  He  died  a  mental 
and  physical  wreck.  You  may  ask  why  I  mention  the  career  of  this  unfor- 
tunate man  as  an  example  of  professional  success.  I  mention  it  not  only  on 
account  of  his  valualile  contributions  to  surgery  for  twenty-five  years,  but 
chiefly  for  the  reason  that  every  act  of  his  generous  life  was,  like  the  imme- 
diate cause  of  his  untimely  death,  inspired  by  an  unmeasured  aiuount  of 
human  sympathy  and  love  for  his  fellowmen. 

Before  closing  I  feel  that  I  must  say  just  a  word  in  regard  to  the  oppor- 
tunities for  professional  success  offered  by  the  laboratory  worker,  the 
investigator,  the  seeker  after  the  great  truths  which  nature  seems  so 
maliciously  to  conceal.  The  poorest  paid  of  all,  this  unselfish  and  self- 
sacrificing  army  of  scientific  workers  seems  content,  without  hope  or  thought 
of  pecuniary  reward,  to  devote  their  lives  to  the  study  of  the  nature  and 
causation  of  disease,  the  etiology  of  infection,  the  pathology  of  new-growths, 
the  underlying  principles  of  immunity,  the  function  of  the  ductless  glands, 
the  synthetic  elaboration  of  remedial  agents,  the  explanation  of  shock,  the 
development  of  new  and  safer  methods  of  anesthesia,  surgical  technic  and 


RAXSOHOFf  MEMORIAL  r GLUME 


the  hundred  other  problems  of  vital  interest  to  the  practitioner.  The  work 
is  arduous,  lime  consuming,  exhausting,  yet  the  rewards  are  great. 

Take  the  life  of  Jenner,  the  English  country  doctor,  living  in  the  last 
century  at  a  time  when  the  great  civilized  centers  of  Europe  were  annually 
devastated  by  the  most  dreaded  of  all  modern  plagues,  epidemic  .smallpox. 
He  made  up  his  niind  to  investigate  its  cause  and,  if  ])ossible,  to  discover  a 
remedy  for  it.  He  began  to  study  it  carefully  from  all  points  of  view,  and 
his  attention  by  a  strange  coincidence  was  quickly  directed  to  a  similar 
disease  which  prevailed  among  cattle.  Mildly  toxic  in  character,  it  was 
accompanied  by  lesions  which  were  almost  identical  with  those  of  smallpox. 
Dr.  Jenner  also  discovered  that  the  people  who  had  care  of  these  cattle,  as 
milkmen  and  stablemen,  were  often  infected  and  presented  small  lesions  on 
their  hands,  and  that  these  people  were  absolutely  and  forever  immune  from 
smallpox.  Then  a  great  idea  entered  his  mind:  if  the  entire  community 
could  be  inoculated  with  this  mild  cowpox,  no  epidemic  of  smallpox  could 
afTect  them.  This  idea  grew  in  the  mind  of  Jenner,  and  developed  into  a 
great  principle  of  medical  therapeutics,  ^^'hen  he  was  bold  enough  to  an- 
nounce his  discovery  before  the  Royal  College  of  Physicians  of  London,  did 
they  receive  it  with  enthusiastic  interest  or  open  minds:  Not  at  all — on  the 
contrary,  they  denounced  Dr.  Jeimcr,  called  him  a  quack,  a  charlatan, 
declared  that  his  methods  were  brutal  and  inhuman  and  should  never  be 
included  in  scientific  medical  jjractice.  Jenner.  however,  jiersisted  in  advo- 
cating protective  vaccination,  and  was  finally  enabled  to  ]irove  the  truth  of 
his  discoveries.  He  died  a  poor  man.  Although  he  de\  oted  the  greater  part 
of  his  professional  life  to  this  great  work,  if  it  had  not  been  for  the  liber- 
ality of  the  British  government  he  would  have  died  in  abject  poverty.  Today 
what  millionaire,  what  multimillionaire,  would  not  give  the  greater  part  of 
his  possessions  for  a  name  and  fame  like  that  of  the  great  Jenner? 

Let  us  turn  for  a  moment  to  the  career  of  Pasteur,  a  trained  chemist, 
who  in  early  life  gave  evidence  of  great  originality  of  thought.  Pasteur 
thought  he  saw  in  fermentation  the  action  of  living  germs,  low  forms  of 
animal  and  vegetable  life.  As  he  studied  fermentation,  he  actually  discov- 
ered in  fermenting  substances  millions  of  these  organisms,  dififering  ifi  size 
and  shape  with  the  various  types  of  fermentation.  Later  he  recognized  that 
the  processes  he  observed  during  the  fermentation  of  inert  matter  were 
similar  to  the  processes  which  take  place  in  human  beings  and  animals  as  a 
result  of  infectious  disease.  Then  a  great  idea  occurred  to  him,  namely,  that 
these  or  similar  micro-organisms  were  the  cause  of  infectious  diseases.  By 
his  logical  reasoning,  his  accurate  methods  of  investigation,  and  his  epoch- 
making  inoculative  experiments,  he  demonstrated  the  great  truth  of  the 
causation  of  contagious  diseases,  namely,  that  they  are  due  to  the  presence 
in  the  blood  and  tissues  of  these  low  forms  of  animal  or  vegetable  life — and 
the  great  germ  theory  of  disease  was  born.  As  a  reward,  did  Dr.  Pasteur 
receive  the  generous  treatment  of  his  medical  colleagues?     Decidedly  not. 

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GEORGE  EMERSON  BREWER 


He  was  more  bitterly  denounced  and  criticized  than  was  Jenner;  but  he 
knew  he  was  right  because  his  methods  were  accurate ;  he  was  convinced 
that  his  logical  deductions  could  not  be  disproven,  and  he  finally  was  able 
to  demonstrate  to  the  scientific  world  that  his  theories  were  absolutely  cor- 
rect, (  )n  the  occasion  of  the  celebration  given  in  honor  of  his  seventieth 
birthday  by  the  French  government,  before  an  enormous  audience  com- 
l)Osed  of  distinguished  men  of  science  from  all  parts  of  the  civilized  world, 
the  great  Lister,  addressing  him,  said:  "You  have  raised  the  veil  which 
for  centuries  has  covered  infectious  diseases.  You  have  discovered  and 
demonstrated  their  microbic  origin."  Dupuy,  a  colleague,  said:  "\\*ho  can 
say  how  much  human  life  owes  to  you,  and  how  much  more  it  will  owe  to 
you  in  the  future."  J.  I'..  Dumas,  his  friend  and  admirer,  said:  "Alay 
I'rovidence  long  spare  yuu  to  France,  and  maintain  in  you  the  admirable 
equilibrium  between  the  mind  that  observes,  the  genius  that  conceives,  and 
the  hand  that  executes  with  a  perfection  and  accuracy  hitherto  unknown." 
Apart  from  his  epoch-making  discoveries.  Pasteur  blazed  the  trail  for  all 
future  investigation  by  demonstrating  the  immense  value  of  painstaking 
accurate  laboratory  methods  in  the  elucidation  of  the  many  biological  and 
pathological  problems  which  have  confronted  and  which  are  today  con- 
fronting the  medical  world.  As  a  result  of  the  powerful  stimulus  given  to 
all  scientific  work  by  his  methods  and  success,  and  the  many  problems  sug- 
gested by  his  demonstration  of  the  microbic  nature  of  infectious  diseases, 
hundreds  of  able  workers  have  been  attracted  to  this  fruitful  field  of  investi- 
gation, and  medicine  has  been  enriched  by  the  masterly  work  of  Koch,  of 
Roux,  of  Behring,  of  Kitasato,  of  Ehrlich.  of  W'idal,  of  \\'right,  of  Welsh, 
of  Flexner,  and  a  host  of  others  equally  distinguished. 

It  is,  however,  to  the  work  of  Lister  that  surgeons  turn  with  sui)crlativc 
pride  and  with  the  greatest  satisfaction.  Practicing  surgery  in  the  jire- 
antiseptic  days,  he  quickly  appreciated  thai  the  greatest  factor  in  the  pre- 
vention of  surgical  progress  was  infection — not  at  that  time  known  by  that 
name  or  understood,  but  recognized  on  every  side  by  its  final  results,  sup- 
puration, wound  fever,  pyemia,  septicaemia,  erysipelas,  hospital  gangrene, 
etc.,  etc.  The  death  rate  from  this  cause  following  surgical  procedures  was 
so  great,  that  only  a  few  necessary  life-saving  operations  were  undertaken, 
as  the  repair  of  severe  injuries,  amputations  for  malignant  disease,  ligation 
of  vessels  for  hemorrhage  or  aneurism,  and  the  occasional  removal  of  dis- 
figuring tumors.  The  death  rate  following  major  amputations  was  upwards 
of  60  per  cent.,  of  strangulated  hernia  40  to  fiO  per  cent.,  of  abdominal  sec- 
lion  almost  100  per  cent.  In  not  a  single  instance  in  one  hundred  years  at 
the  \'ienna  Maternity  Hospital  had  a  woman  survived  Csesarean  section,  an 
operation  }ou  will  fre(|uently  see  at  the  Sloane  Hospital  with  practically  no 
mortality.  Nelaton.  who  was  in  despair  during  the  siege  of  Paris,  at  the 
sight  of  the  death  df  nearly  every  patient  operated  upon  at  the  Grand  Hotel, 
then  a  temporary  military  hospital,  declared  that  the  surgeon  who  could  con- 


RANSOHOFf  MEMORIAL  VOLUME 


qiier  purulent  wound  infection  would  be  deserving  of  a  golden  statue.  Lis- 
ter's great  mind  saw  in  Pasteur's  work  an  explanation  of  surgical  infection. 
He  believed  septic  disease  to  be  due  to  the  presence  in  the  tissues  of  patho- 
genic bacteria,  and  he  conceived  the  great  idea  that  if  those  micro- 
organisms could  be  excluded,  primary  healing  without  fever  or  other  unfa- 
vorable symptoms  would  occur.  Then  followed  years  of  arduous  experi- 
mental work,  in  which  he  was  hampered  and  harrassed,  not  only  by  pro- 
fessional criticism  and  ridicule,  but  by  the  action  of  the  British  government, 
which,  yielding  to  the  antivivisection  clamor,  enacted  legislation  which  prac- 
tically prevented  his  continuing  this  great  work  on  English  soil.  Un- 
daunted by  this  hostile  action  he  transported  his  laboratories  to  France,  and 
there,  amid  more  favorable  conditions,  he  completed  his  great  work.  In 
giving  to  the  world  a  method  of  operating  by  which  sepsis  can  be  avoided. 
Lister's  discovery  must  be  regarded  not  only  as  the  greatest  contribution  to 
surgery  of  this  century,  but  as  the  greatest  advance  in  surgical  therapeutics 
of  all  centuries,  the  greatest  life-saving  measure  of  all  time;  for  it  not  only 
removed  the  terrific  death  rate  of  the  few  operative  procedures  then  em- 
ployed, but  it  opened  up  the  vast  field  of  modern  surgery,  which  has  resulted 
in  the  relief  and  cure  of  scores  of  diseases,  which  without  the  aid  of  modern 
surgery  led  only  to  death,  prolonged  sufifering.  or  chronic  invalidism.  So 
long  as  the  human  race  suflfers  from  injury  or  surgical  disease,  so  long  as 
surgery  is  practiced  or  taught,  so  long  will  the  name  of  Lister  be  known  and 
justly  spoken  of  as  one  of  the  greatest  benefactors  of  mankind. 

Gentlemen,  T  have  attempted  in  this  informal  t.nlk  to  give  von  an  idea 
of  the  standards  of  professional  success  which  m.Tv  be  attained  in  addition 
to  the  gaining  of  a  livelihood.  Not  that  I  would  for  a  moment  belittle  the 
latter  aim,  for  the  workman  in  medicine  is  certainlv  worthy  of  his  hire.  Rut 
if  vou  practice  your  profession  ethically,  with  intelligence,  with  skill  and  with 
a  large  measure  of  human  sympathy  and  philanthronv.  you  will  never 
receive  in  dollars  and  cents  anything  like  an  equivalent  of  the  services  vou 
render:  yet  it  lies  within  the  power  of  each  one  of  you  to  attain  a  profes- 
sional success  which  will  be  satisfying  directly  in  proportion  to  your  activities. 

The  profession  you  have  chosen  is  an  honor.nble  one.  its  Iiistory  and 
traditions  are  inspiring,  its  accomplishments  are  deserving  of  the  greatest 
praise,  but  to  succeed  in  it  you  must  be  prepared  to  give  it  your  best 
efiforts,  your  unceasing  devotion,  your  undivided  attention — you  must  make 
it  in  reality  your  life  work.  Remember,  however,  that  the  path  to  success 
is  not  an  easy  one:  discouragement,  failure,  and  criticism  often  virulent  and 
unmerited  will  be  vour  lot,  if  vou  leave  the  lieaten  track  and  seek  to  estab- 
lish new  priiu-iplcs,  or  advocate  methods  not  sanctioned  by  tradition.     Let 


Page  eg 


GEORGE  EMERSON  BREWER 


me  urge  )ou,  however,  in  your  periods  of  discouragement  and  trial  to  bear 
ill  mind  the  words  of  the  poet : 

"One  ship  drives  east  and  another  west, 
\\'hile  the  self-same  breezes  blow. 
It's  the  set  of  the  sails  and  not  the  gales 

That  bids  them  where  to  go. 
Like  the  winds  of  the  sea  are  the  ways  of  the  fates, 

As  we  voyage  on  through  life; 
It's  the  set  of  the  soul  tiiat  determines  the  goal. 
And  not  the  storms  and  the  strife." 

George  Emerson  Brewer. 


MLXTirLE  IXFECTIONS. 
Bv  Mark  A.  Brown.  M.  D. 


L'litil  within  comparatively  recent  years  the  presence  of  two  or  more 
infectious  processes  existing  in  the  same  individual  at  the  same  time  was 
looked  upon  with  a  considerable  degree  of  skepticism  to  say  the  least. 
Whether  it  was  thought  that  because  of  the  existence  of  a  certain  infec- 
tious disease,  a  particular  antitoxin  was  introduced  or  generated  within 
the  body  that  exerted  an  action  antagonistic  to  the  activity  of  other  germs. 
or  what  not,  I  do  not  presume  to  say.  Indeed,  I  am  not  prepared  to  say  that 
under  certain  circumstances,  among  certain  germs  or  infectious  processes, 
this  antagonistic  action  docs  not  take  place;  it  opens  up  a  field  of  specula- 
tion and  theorizing  too  wide  for  me  to  attempt  here.  Aly  object  to-night  is 
simply  to  place  on  record  a  few  cases  of  multiple  infection,  cases  in  which 
there  could  he  no  doubt  but  that  two  or  more  infectious  processes  were 
actively  at  work  in  the  same  individual  at  the  same  time.  In  the  first  place,  it 
must  be  assumed — and  we  have  all  of  us  accepted  it  probably  long  ago — 
that  there  are  certain  diseases  which  must  be  classed  as  infectious,  in  which 
no  germ  has  as  yet  been  isolated,  that  therefore  do  not  conform  to  Koch's 
laws,  but  concerning  which  there  can  exist  no  uncertainty  in  the  minds  of 
those  willing  to  accept  the  germ  theory,  but  that  they  are  dependent  upon  a 
specific  organism.  I,  of  course,  refer  among  others  to  certain  of  the  infec- 
tious diseases  of  childhood,  to  syphilis,  and  to  the  disease  that  brought  out 
that  most  interesting  paper  of  last  ^Tonday  night — acute  inflammatory  rheu- 
matism. 

CASE  I. 
SYPHILIS  AXD  VACCINIA. 

Patient,  a  male,  aged  28,  unmarried,  of  good  physique,  well  developed 
and  nourished.  He  was  first  seen  on  March  16.  1900.  coming  to  me  to  be 
vaccinated.  The  vaccination  "took"  in  the  usual  time  and  began  to  pass 
through  the  usual  changes.  On  the  seventh  day  after  the  inoculation  he 
came  again  and  called  my  attention  to  an  eruption  that  had  invaded  the  sur- 
face of  the  body  pretty  .generally,  with  the  exception  of  the  face.  It  was 
present  to  a  slight  degree  both  upon  the  palms  of  the  hands  and  the  soles 
of  the  feet.  The  eruption  was  most  decidedly  of  a  copper  hue,  and  was  not 
actively  inflammatory  in  type^that  is  to  say.  the  skin  around  each  indi- 
vidual lesion  was  not  at  all  hyperemic.  It  was  distinctly  a  psoriasis,  and 
this,  combined  with  the  marked  copper  color  and  the  involvement  of  the 
hands  and  feet,  led  me  to  the  opinion  that  it  was  syjjhilitic.  Indeed,  that  was 
also  his  idea,  for  he  freelv  admitted  that  lie  had  had  a  hard  chancre  about 


MARK  A.  BROWN 


two  years  previously,  which  had  been  followed  by  a  general  cutaneous  erup- 
tion and  later  by  some  ulcers  in  the  mouth.  He  had  carried  out  his  treat- 
ment in  rather  a  desultory  manner,  but  there  had  been  no  recurrence  of 
eruption  until  the  present  time.  He  brought  up  the  question,  which  has  since 
puzzled  me,  if  the  vaccination  could  have  caused  a  flare-up  of  his  syphilis. 
The  pock  on  his  arm  pursued  the  usual  course,  not  severe,  and  scar  forma- 
tion took  place  in  the  usual  time.  At  no  time  was  there  any  pustular  erup- 
tion present,  or,  indeed,  any  other  than  the  psoriasis  I  have  mentioned.  He 
was  ordered  mercurial  inunctions  and  the  eruptions  responded  immediately, 
though  at  the  end  of  two  weeks  there  could  still  be  seen  very  faint  copper- 
colored  stains, 

CASE  II. 
I'STIVO-.VUTU.MKAL  M-\I.-\RIA  .\XD  PULMOXAKV  TUBERCULOSIS. 

Albert  13.,  male,  aged  25,  a  native  of  Tennessee.  About  two  years  ago 
he  left  the  mountains  where  he  had  been  raised  and  went  to  Texas.  While 
there  he  contracted  malaria  of  rather  a  severe  form,  which  responded  rather 
slowly  to  treatment.  When  not  constantly  under  the  influence  of  quinine 
the  chills  and  fever  would  return,  so  that  he  was  finally  advised  to  return 
home,  which  he  did.  In  all  he  was  in  Texas  nine  months.  On  returning 
home  he  improved  slowly  and  steadily  until  about  four  months  ago,  when  he 
began  to  lose  in  weight  and  to  suffer  from  occasional  chills,  though  no 
actual  rigors.  He  complained  mostly  of  weakness  and  of  severe  diarrhea, 
the  latter  often  accompanied  by  great  abdominal  pain.  His  appetite  was 
capricious ;  there  were  occasional  attacks  of  vomiting.  He  was  finally 
brought  to  Cincinnati,  and  I  first  saw  him  at  9:30  a.  m..  May  12,  1902.  I 
mention  the  time  of  day,  as  on  taking  his  temperature  during  the  examina- 
tion that  followed  it  was  found  to  be  normal.  Particularly  manifest  was 
the  grave  anemia,  which,  combined  with  the  peculiar  lemon-yellow  tint  of 
his  skin,  brought  immediately  to  mind  pernicious  anemia ;  however,  with  the 
clear  history  of  malaria  given,  this  opinion  was  not  long  entertained,  though 
there  is  no  reason  why  the  two  could  not  exist  together,  some  authorities, 
indeed,  giving  malaria  as  one  of  the  causes  of  pernicious  anemia.  The  tem- 
jierature,  as  has  been  said,  was  normal ;  the  ])ulse  about  100,  of  low  tension 
and  markedly  dicrotic  ;  as  indications  of  the  anemia,  the  feet  and  ankles  were 
markedly  edematous.  The  lungs  were  not  examined  at  that  time,  as  there 
was  absolutely  no  history  that  would  lead  one  to  believe  that  they  were 
involved.  A  superficial  examination  of  the  heart  revealed  a  slight  systolic 
murmur,  which  was  ascribed  to  the  anemia.  He  was  sent  at  once  to  the 
Presbyterian  Hospital,  with  orders  as  to  treatment. 

.\s  I  had  to  leave  the  city  that  afternoon  I  did  not  see  him  until  the 
morning  of  the  14lh,  when  the  first  blood  examination  was  made.  The  blood 
when  drawn  from  tiie  ear  showed  little  tendency  to  coagulate.  Examination 
of  the  fresh  unstained  blood  showed  the  plasmodium  of  Laveran  after  about 
five  minutes'  search.     The  first  three  specimens  were  quite  small,  rounded. 


RAXSOHOFF  MEMORIAL  VOLUME 


with  most  of  the  pigment  at  the  periphera,  no  portion  of  red  corpuscle 
remaining.  The  jjigment  granules  were  small,  hut  such  as  were  toward  the 
center  showed  movement,  though  sluggish.  The  fourth  specimen  was  an 
egg-shaped  corpuscle  with  one  pole  occupied  hy  the  parasite,  in  which  latter 
movement  of  the  pigment  granules  was  distinctly  \isible.  Dr.  Oliver  and 
the  internes  who  afterwards  examined  the  slide  told  me  that  they  had  found 
crescents,  which  were  what  I  myself  had  been  particularly  in  search  of. 
There  was  no  poikilocytosis.  There  was  some  free  pigments  in  the  blood 
and  the  few  leucocytes  seen  were  markedly  pigmented. 

The  diagnosis  of  estivo-autumnal  malaria  was  made  and  quinine  ordered; 
the  slight  effect  of  the  latter  treatment  can  be  seen  by  the  most  casual  inspec- 
tion of  the  temperature  chart.  It  will  also  be  noted  from  the  temperature 
chart  that  the  rise  always  began  about  noon  and  continued  throughout  the 
afternoon  and  evening — hectic,  indeed  ;  while  in  malaria  it  has  been  my 
experience  to  have  the  paroxysm  in  the  morning,  though  of  course  this  is 
not  always  the  case.  I  was  satisfied  that  estivo-autumnal  malaria  was  pres- 
ent in  this  case,  and  malaria  of  this  nature  is  usually  accompanied  by  a  mild 
continued  or  slightly  remittent  fever,  or  in  chronic  cases,  in  which  few 
organisms  are  present,  as  in  the  one  under  consideration,  l)y  no  fever  at  all. 
In  this  case,  too,  the  rise  of  temperature  was  never  accompanied  by  chills. 
Lastly,  there  was  the  total  failure  of  response  to  ciuinine ;  I  have  always 
believed  the  dictum  that  any  intermittent  fever  which  does  not  in  three  or 
four  days  respond  to  quinine  is  not  malarial.     I  knew  positively  that  estivo- 


MARK  A.  BROWN 


autumnal  malaria  was  present — the  typical  specimens  showed  that — though 
it  was  rather  unusual  to  find  the  regular  intra-corpuscular  parasites  and  the 
crescents  in  the  same  peripheral  field ;  then,  too,  as  indicated  before,  one 
would  not  expect  from  the  examination  of  the  blood  a  fever  of  the  type  here 
shown.  The  natural  conclusion  was  that  there  was  another  lesion  present 
that  liad  been  overlooked.  It  was  not  hard  to  find;  examination  of  the  left 
apex  of  the  lung  revealed  dullness,  and  immediately  under  the  clavicle,  at 
about  its  center,  was  well-marked  cavernous  breathing.  The  cavity  was  quite 
small.  A  few  mucous  rales  were  present  over  the  left  lung,  extending  to  about 
the  fourth  rib.  Posteriorly  these  rles  could  be  heard  extending  to  the  upper 
level  of  the  infra-scapular  fossse.  That  was  all.  surely  not  enough  to  account 
for  the  great  loss  of  weight — about  60  pounds — and  strength,  and  the  pro- 
found anemia  (the  blood  count  was  about  2,800,000),  all  within  the  space 
of  not  over  four  months.  On  questioning  the  nurses  in  charge,  it  was 
learned  that  he  had  coughed  but  rarely,  and  ex])ectoration,  on  reference  to 
his  spit-cup,  occurred  but  four  or  five  times  in  the  twenty-four  hours.  I^e 
himself  was  so  little  annoyed  by  these  latter  symptoms  that  he  had  not 
thought  it  worth  while  to  mention  them  to  me.  The  examination  of  the 
sputum  revealed  tubercle  bacilli  in  large  numbers,  as  well  as  an  abundance 
of  the  germs  of  suppuration.  The  examination  of  the  urine  was  entirely 
negative.  The  stools  were,  as  a  rule,  loose,  sometimes  of  a  greenish  color, 
and  often  containing  mucous.  The  liver  was  markedly  enlarged,  the  s])leen 
less  so. 

It  seems  to  me,  in  the  explanation  of  this  case,  that  the  lessened  vitality 
caused  by  the  invasion  of  the  plasmodium  so  lowered  bis  resisting  power 
that  he  was  unable  to  withstand  the  onslaught  of  the  tubercle  bacillus,  even 
though  assisted  by  a  pure  mountain  air,  good  hygienic  surroundings,  and  the 
best  of  good  country  food. 

This  case  has  been  of  particular  interest  to  me  in  \iew  of  the  fact  that 
every  year  probably  thousands  of  cases  of  early  phthisis  are  called  malaria ; 
the  combination  of  the  two  diseases  in  the  same  individual  is,  I  believe,  a 
little  unusual,  at  least  it  is  the  first  case  of  the  kind  that  has  been  brought 
to  my  attention.  I  do  not  believe,  in  view  of  the  absence  of  response  of 
fe\Tr  to  quinine  and  the  few  parasites  found,  that  the  fever  was  in  any  way 
dependent  upon  the  malarial  infection  ;  the  chart  shows  it  to  be  a  typical 
example  of  that  fever  occurring  during  the  first  few  months  of  phthisis,  the 
so-called  fever  of  tuberculization.  I  might  say,  in  conclusion,  that  after  a 
week's  use  of  the  quinine  the  parasites  could  no  longer  be  found  in  the 
peripheral  blood  and  the  size  of  the  spleen  was  markedly  reduced. 

CASE  III. 

WHOOPING  COUGH,  .ACUTE  INFLAMMATORY  RHEU.MATISM,   LOBAR 

PNEUMONIA. 

The   prexious   hist(iry   in   this  case  is  of   some   importance.     The   older 

brother  of  my  patient  is  aged  25,  is  married,  and  lives  in  Newport,  Ky.     He 


RAXSOHOFF  MEMORIAL  VOLUME 


came  to  m_v  office  Februar}'  \i,  1902,  suffering  from  acute  follicular  tonsil- 
litis. He  thought  that  there  might  be  some  di])htheria  connected  with  his 
case,  so.  afraid  of  infecting  his  infant  son,  he  determined  to  go  to  his  moth- 
er's home  in  Cincinnati.  He  was  well  in  a  few  days,  but  about  a  week  after 
1  first  saw  him,  a  younger  Ijrother,  aged  14.  also  living  with  the  mother,  was 
taken  down  with  a  similar  trouble,  and  in  another  week  the  youngest 
brother,  aged  8.  On  April  3  I  was  called  to  see  the  fourteen-year-old  boy, 
Frank,  and  found  him  suffering  from  acute  inflammatory  rheumatism  affect- 
ing the  right  ankle ;  next  day  it  had  moved  over  to  the  left.  Under  combined 
salicylate  and  alkaline  treatment  he  rai)idly  convalesced  without  cardiac 
lesion  or  involvement  of  other  joints. 

On  April  6  I  was  asked  to  see  H.  ^.,  me  eight-year-old  child  and  the 
subject  of  the  present  report.  He  was  suffering  from  a  mild  fever  and 
rather  a  severe  cough,  not  in  any  way  spasmodic,  while  on  physical  exam- 
ination there  was  but  a  mild  bronchitis  present.  On  April  12  the  fever  rose 
rapidly  and  he  complained  of  severe  pain  in  the  right  ankle  and  shoulder. 
Examination  showed  the  shoulder  to  be  exceedingly  painful  and  tender, 
though  J  could  detect  no  swelling;  the  ankle,  however,  showed  all  the  evi- 
dences ot  an  acute  inflammation.  The  ne.xt  day  the  other  ankle  was  involved, 
the  disease  then  transferring  itself  to  the  wrists  and  fingers.  He  also 
resiJonded  to  the  combined  treatment.  ( )n  .•\pril  14  the  cough  becaiue  dis- 
tinctly paroxysmal,  the  child  having  about  eighteen  to  twenty  attacks  in  the 
twenty-four  hours;  the  attacks  occurred  mostly  at  night  and  in  the  early 
morning  hours,  and  ended  in  the  typical  whoop.  I  heard  him  in  several  of 
his  paroxysms,  and  there  could  be  no  doubt  as  to  the  existence  of  whooping- 
cough.  Belladonna  was  given  and  pushed  to  dilatation  of  the  pupils,  with 
the  results  so  far  as  lessening  the  number  and  severity  of  the  attacks  was 
concerned.  On  April  30  another  rise  of  temperature  super\ened,  soon  fol- 
lowed by  dullness  and  bronchial  breathing  in  the  lower  right  lung.  The 
examination  of  the  sputum  revealed  the  diplococcus  of  Fraenkel.  Crisis 
occurred  on  the  fifth  day  of  the  disease,  and  convalescence  from  his  triple 
infection  proceeded  rapidly,  I  have  seen  both  of  the  younger  children  since 
their  recovery  on  several  occasions,  and  as  yet  there  is  not  the  slightest 
evidence  of  any  cardiac  involvement. 

This  case  has  interested  me  because  of  the  ajiparent  casual  relation  exist- 
ing between  the  tonsillitis  and  the  inflammatory  rheumatism ;  I  have  observed 
this  relation  often,  though  perhaps  never  in  so  satisfactory  manner  as  in  the 
present  case.  Osier,  in  speaking  of  the  relations  of  pneumonia  and  rheu- 
matism, luakes  the  following  statements:  "The  arthritis  may  precede  the 
onset,  and  the  pneumonia,  possibly  with  endocarditis  and  pleurisy,  may 
occur  as  a  complication  of  the  rheumatism.  In  other  instances,  at  the  height 
of  an  ordinary  pneumonia,  one  or  two  joints  may  become  red  and  sore.  On 
the  other  hand,  after  the  crisis  has  occurred  pains  ;uid  swelling  m;iy  come 
on  in  the  joints." 

Pai)c  m 


MARK  A.  BROWN 


CASE  IV. 
TYPHOID   FEVER   AND   SINGLE  TERTIAX   MALARIA. 

The  term  typho-malarial  fever  has  been  in  common  use  in  medical  litera- 
ture for  many  years,  and  even  at  present  one  occasionally  encounters  it.  It 
was  supposed  in  past  years  that  there  occurred  a  combination  of  the  typhoid 
and  malarial  poisons — a  community  of  interests  or  trusts,  as  it  were — and 
that  this  new  combine  manifested  itself  in  "ways  that  are  dark  and  tricks 
that  are  vain,"  however,  to  the  complete  baffling  of  the  common  people, 
/.  c,  the  physician.  The  latter,  however,  boldly  came  to  the  front  and  an- 
notmced  with  pride  that  the  new  combine  manufactured  a  product  that, 
when  poured  out  into  the  '^vsicm,  caused  a  continued  fever  with  marked 
remissions  which  was  extremely  resistant  to  quinine.  This  was  satisfactory 
to  all  concerned  with  the  exception  of  the  poor  patients,  who  didn't  count, 
as  they  always  have  to  suffer  in  the  cause  of  science,  anyway,  so  they  were 
deluged  with  quinine  until  their  ears  rang  and  rang  again  and  they  were 
deaf  to  their  own  entreaties.  Laveran's  discovery  of  the  Plasmodium 
malaria?  straightened  matters  considerably,  and  the  introduction  of  the  agglu- 
tination test  of  Pfeiffer-Widal  completed  the  route  of  th.  Typho-Malaria 
Trust.  Chills,  with  the  added  phenomena  of  heightened  fever  and  sweats, 
are  not  at  all  uncommon  at  any  stage  of  typhoid  fever.  The  disease  may  be 
ushered  in  with  a  chill,  though  this  is  rare.  During  the  course  of  the  disease 
chills  may  be  the  premonition  of  some  such  complication  as  pneumonia, 
pleurisy,  otitis,  periostitis  or  perforation  ;  or  they  may  follow  a  too  vigorous 
use  of  coal-tar  derivatives,  particular  guaiacol  locally  applied  to  the  abdo- 
men. During  convalescence — and  these  are  the  cases  to  which  the  term 
typho-malaria  is  so  often  misapplied — they  may  occur  bearing  no  relation 
to  the  above-mentioned  causes,  but  from  reasons  not  entirely  understood, 
though  probably  dependent  upon  septic  infection  or  autointoxication,  as 
when  the  bowels  have  been  allowed  to  remain  confined  for  several  days. 
Hov/ever,  a  coincident  infection  with  the  malarial  parasite  may  occur  at 
any  time  during  the  typhoid  attack,  though  it  is  rare,  and  a  positive  diag- 
nosis must  not  be  made  without  finding  the  Plasmodium  in  the  blood.  In 
most  cases  there  has  been  a  previous  malarial  attack,  and  the  flare-up  of 
the  latter  occurs  during  the  typhoid  convalescence. 

P.  K.,  Jr.,  aged  24,  a  native  of  Cincinnati,  and  has  lived  in  this  neigh- 
borhood all  his  life.  Was  first  seen  on  May  10,  1900.  Previous  history 
negative,  aside  from  the  ordinary  diseases  of  childhood  and  an  attack  of 
chills  and  fever  a  year  ago,  which  had  promptly  responded  to  quinine. 
^^l^en  I  first  saw  him  he  had  been  sick  about  a  week  with  the  usual  initial 
symptoms  of  typhoid  fever,  including  the  nose-bleed.  In  a  few  davs  the 
spleen  could  be  palpated  and  rose-spots  developed  upon  the  abdomen.  The 
Widal  reaction,  made  several  times,  was  positive.  The  attack  was  quite  a 
mild  one  and  was  unaccompanied  by  chills  until  convalescence  was  well 
established.    Indeed,  the  attack  was  so  light  that  it  was  not  found  necessary 


RAXSOHOFf  MEMORIAL  VOLUME 


to  adopt  any  antipyretic  measures,  though  the  temperature  did  on  several 
occasions  exceed  103  degrees.  (I  have  found  that  among  people  of  ordinary 
inteUigence  a  fairly  reliable  temperature  record  can  be  kept,  whicli  can.  if 
found  necessary,  be  subsequently  charted ;  and  I  have  made  it  a  rule  in 
fevers  to  appoint  some  reliable  member  of  the  family  to  take  the  tempera- 
ture regularly,  as  was  fortunately  done  in  this  case.)  When  the  evening 
temperature  approached  the  normal,  visits  were  made  late  in  the  afternoon, 
so  that  the  evening  temperature  at  least  could  be  verified.  (In  the  evening 
of  May  28,  convalescence  having  been  well  established,  the  temperature 
was  found  to  be  101.8  degrees.  The  mother  told  me  that  the  boy  had  had 
a  slight  chill  at  ten  that  morning,  and  that  his  temperature  had  gone  to 
103.8  degrees  by  noon.  He  had  then  broken  out  into  a  sweat,  and  by 
3  :00  p.  m.  the  fever  had  dropped  to  102.6  degrees.  The  next  morning  the 
temperature  was  normal,  and  I  obtained  a  fresh  specimen  of  blood,  which 
was  found  to  contain  an  abundance  of  half-grown  tertian  malarial  parasites. 
He  had  no  chill  that  day.  and  the  evening  temperature  was  but  99.2  degrees. 
He  was  ordered  ten  grains  of  the  bisulphate  of  quinine,  to  be  given  at 
eight  the  following  morning.  The  chill  occurred  at  about  10:15  a.  m.,  the 
temperature  going  to  103.4  degrees  by  noon.  Quinine  bisulphate  was  then 
ordered  in  four-grain  doses  three  times  a  day.  with  a  resulting  disappear- 
ance of  the  malaria.  As  said  liefore,  the  typhoid  had  about  run  its  course, 
so  that  the  patient  was  soon  able  to  be  discharged.  He  has  iiad  one  attack 
of  malaria  since  that  time. 

In  this  case  there  was  a  coincident  typhoid  and  malaria  infection.  The 
diagnosis  of  typhoid  was  made  by  the  history,  the  enlarged  spleen,  the  char- 
acter of  the  fever,  the  rose  spots  and  the  W'idal  reaction.  The  diagnosis  of 
single  tertian  malaria  was  made  by  the  occurrence  of  morning  chills  and 
rigors  every  third  day.  the  finding  of  tyjiical  tertian  organisms  in  the  blood 
and  the  therapeutic  test. 


DISINFECTION   OF  THE   KNEE   JOINT.* 

ROBKRT  P..  COFII-LD.  M.  D. 
Cincinnati. 

^^'hether  in  civil  or  military  practice,  it  is  generally  conceded  that  sejjtic 
infection  of  the  knee  joint  is  one  of  the  most  serious  conditions  that  the 
surgeon  can  he  called  on  to  treat,  endangering,  as  it  does,  both  the  future 
usefulness  of  the  joint,  and  at  times,  the  very  life  of  the  individual. 

In  civil  experience  we  have  formerly  been  led  to  a  profound  distrust  of 
the  ability  of  this  particular  articulation  to  deal  with  infective  processes.  In 
septic  arthritis,  an  arthrotoniy  was  usually  advised  and  drainage  tubes  or 
wicks  were  inserted  into  the  joint  cavity,  or  through  and  through  drainage 
was  established  and  the  tubes  allowed  to  remain  for  at  least  a  number  of 
days.  Besides  producing  an  evil  mechanical  effect  on  the  synovia  and  carti- 
lages, the  drainage  material  provided  an  ideal  reservoir  for  the  pabulum  in 
which  the  organisms  could  multiply  and  travel  from  within  outward.  si)read- 
ing  infection  to  the  para-articular  structures,  or  from  without  inward,  carry- 
ing secondary  infection  from  the  skin  into  the  joint  cavity. 

The  anatomic  structure  of  the  knee  joint  is  such  that  when  it  is  severely 
infected  over  its  whole  extent,  drainage  becomes  a  serious  and  difficult 
matter,  and  even  though  skilfully  done,  it  is  a  most  unsatisfactory  proced- 
ure, often  resulting  in  the  tracking  of  the  infection  along  the  muscular  and 
fascial  planes,  above  or  below  the  joint,  with  the  accompanying  dangers  of 
septicopyemia  and  severe  damage  to  the  joint  structures,  resulting  in  anky- 
losis. 

COXDITIOXS  XECESS-ARV  FOR  F.AVOR.-XBLE  RESULTS, 
The  results  achieved  in  the  present  war,  in  treating  infected  wounds 
of  the  knee  by  disinfection  and  immediate  closure,  have  been  the  source  of 
much  surprise  and  satisfaction.  Favorable  results,  however,  with  restora- 
tion of  joint  function,  seem  to  depend  on  the  observance  of  certain  princi- 
ples which  are  doubtless  of  equal  importance  in  treating  septic  arthritis  of 
autogenous  origin : 

1.  The  operation  must  be  done  early,  before  the  spread  of  infection  and 
the  disorganization  of  the  joint  structures  have  had  time  to  occur. 

2.  Thorough  lavage  of  the  infected  and  contaminated  areas,  followed  by 
primary  closure  of  the  joint  capsule,  is  essential. 

3.  Foreign  bodies  must  not  be  allowed  to  remain  within  the  joint  cavitv. 

4.  When  drainage  is  used  at  all,  it  should  be  carried  down  to  the  cajisule, 
but  not  into  the  joint  cavity. 

5.  Immobilization  of  the  joint  must  be  secured  by  adequate  mechanical 
fixation. 

•Read  before  the  Sectifm  on  Orthopedic  .Suruery  .it  the  Si.\tv-ninth  .\nnua1  Session  of  the 
American  Medical  Association.  ChicaKo,  lune.  1918.  From  the  lournal  of  the  .American  .Medical 
Association,    October    19,    1918. 


RANSOHOFf  MEMORIAL  VOLUME 


In  order  for  a  surgeon  to  carry  out  these  principles  effectually,  it  is  of  the 
utmost  importance  that  a  diagnosis  of  suppurative  arthritis  be  made  early  in 
the  course  of  infection.  This  is  not  often  difficult,  since  the  joint  involve- 
ment usually  accompanies  or  follows  a  focal  or  general  infection,  originating 
elsewhere  in  the  body,  such  as.  gonorrhea,  tonsillitis,  otitis  media,  scarlet 
fever,  pneumonia,  etc. 

This  form  of  arthritis  may  be  secondary  to  a  serous  synovitis  or  it  may 
start  without  any  obvious  serous  stage.  The  septic  joint  is  often  ushered  in 
with  a  chill,  the  temperature  is  elevated,  the  capsule  becoines  distended  with 
fluid,  and  the  joint  is  inflamed  and  jiainful  and  is  held  in  a  semiflexed  posi- 
tion b\'  the  spasmodically  contracted  muscles. 

Every  joint  that  shows  evidence  of  inflammation  and  eft'usion.  during  the 
course  of  a  focal  or  general  infection  or  following  it  should  be  aspirated 
under  strictly  aseptic  precautions  for  diagnostic  purposes.  The  nature  of  the 
aspirated  fluid  will  be  a  very  definite  guide  as  to  the  proper  course  to  pursue. 

The  bacteriologic  side  of  the  investigation  so  often  fails  to  reveal  the 
presence  of  micro-organisms  in  the  joint  fluid,  either  in  smears  or  cultures, 
that  considered  by  itself,  it  carries  little  weight,  and  negative  findings  in  this 
regard  should  not  influence  the  course  of  our  treatment. 

The  cytologic  investigation  of  the  joint  fluid,  however,  is  a  distinct  aid 
to  the  diagnosis,  and  at  times  will  materially  influence  the  prognosis,  in  joint 
eft'usions.  A  high  percentage  of  polymorphonuclear  leukocytes  found  in  a 
sample  of  the  aspirated  fluid  will  afford  positive  evidence  of  a  septic  condi- 
tion. The  normal  synovial  fluid  from  the  knee  joint  is  acellular.  Pus.  which 
consists  of  practically  100  per  cent,  polymorphonuclear  leukocytes,  is  a 
surgically  visible  sign  that  infection  of  the  part  has  occurred  and  calls  for 
prompt  surgical  intervention. 

TF.CHXIC  OF  DISIXFF.CTIOX. 

The  technic  which  1  lia\e  followed  in  disinfecting  the  knee  joint  is 
briefly  as  follows : 

The  knee  joint  is  prepared  the  day  previous  to  operation  by  being  shaved 
and  scrubbed  and  wrapped  in  sterile  dressings.  After  the  patient  is  anesthe- 
tized, the  field  of  operation  is  further  sterilized  with  benzin  and  iodin.  An 
incision  l_^-2  or  2  inches  long  is  made  parallel  to  the  inner  or  outer  border 
of  the  ]5atella,  extending  into  the  joint  cavity.  If  found  desirable  this  incis- 
ion may  be  extended  to  facilitate  a  more  complete  ex])loration  of  the  joint. 
By  means  of  a  gravity  .syringe,  placed  high  enough  to  give  the  stream  con- 
siderable pressure,  the  joint  cavity  is  now  thoroughly  flushed  for  fifteen  or 
twenty  minutes.  Instead  of  using  the  sterile  glass  tip.  commonly  attached 
to  the  tubing  leading  from  tlie  container,  it  is  better  for  the  operator  to  use 
a  soft  rubber  tip  which  may  be  inserted  into  the  various  recesses  of  the  j(;int 
without  the  danger  of  injuring  their  delicate  lining. 

\'arious  solutions  have  been  used  with  success  for  disinfection  of  septic 
joints.     Some  operators  even  assert  that  the  results  do  not  depend  on  the 

I'aof  12 


ROBERT  B.  COFIELD 


nature  of  the  solution  employed,  but  rather  that  it  is  the  thorough  mechanical 
cleansing  which  is  the  important  factor.  However,  since  it  has  been  shown 
that  the  synovia  and  cartilage  withstand  very  well  the  active  disinfecting 
agents,  and  since  the  pathotjcnic  organisms  are  harbored  within  the  synovia 
and  para-articular  iis-ut>.  and  not  in  the  joint  cavity,  I  prefer  to  use  an 
active  disinfectant  which  pu>sesses  a  penetrating  as  well  as  a  cleansing  action. 
Mercuric  chlorid,  1  :  15,C00,  in  salt  solution,  as  suggested  by  Dr.  Cotton  of 
Boston,  maintained  at  a  temperature  of  about  115  F.  and  this  followed  by 
physiologic  sodium  chlorid  solution,  has  proved  very  satisfactory. 

Since  the  capacity  of  the  synovial  cavity  of  the  knee  joint  reaches  its 
maximum  when  the  leg  is  flexed  to  an  angle  of  about  25  degrees,  and  since 
the  conients  of  some  of  the  bursae  communicating  with  the  joint  are  most 
easily  emptied  when  the  limb  is  in  a  semi-flexed  position,  it  is  very  impor- 
tant that  flexion  and  extension  of  the  juint  should  be  jjassixflv  carried  out 
while  the  cavity  is  being  flushed.  'I'his  will  aid  materially  in  ridding  the 
joint  of  the  necrotic  material  and  pus  that  have  accumulated  in  these  various 
pouches.  It  is  also  advisable  repeatedly  to  press  the  edges  of  the  wound 
close  about  the  tip  of  the  syringe  in  order  that  the  fluid  may  tlistend  the  joint 
capsule  and  penetrate  and  flush  out  its  various  recesses. 

The  objects  sought  by  arthrotomy  and  irrigation  of  the  joint  ca\ity  are: 

1.  Relief  of  the  intra-articular  tension,  which  d(iubtk-»  has  a  deleterious 
effect  on  the  svnovial  membrane  and  cartilages  Ibrougli  its  interference  with 
the  circulation  and  the  normal  secretory  fiuiction  of  the  synovia. 

2.  The  removal  of  the  necrotic  material  which  acts  as  a  culture  medium 
within  the  joint  cavity.  The  nature  of  this  material  i>recludes  its  removal 
by  means  of  the  trocar  or  an  aspirating  syringe. 

3.  The  cleansing  and  disinfecting  action  on  the  synovia,  which  aids  it 
materially  in  regaining  a  normal  function  and  renewing  its  fight  against 
infection.  The  synovial  membrane,  like  other  serous  membranes,  has  an 
enormous  capacity  for  combating  infection  if  it  is  a  fairly  normal  condition. 

After  disinfection,  the  capsule  is  closed  with  catgut  sutures,  and  if  a 
drain  is  used  at  all,  it  is  placed  outside  the  synovial  meiubrane  for  the  sole 
purpose  of  taking  care  of  the  extracai^sular  infection.  The  wound  is 
closed  in  layers  and  the  joint  is  thoroughly  inimoliilized,  preferablv  bv  a 
plaster-of-Paris  spica  including  the  foot. 

A  fenestra  may  be  cut  over  the  knee  and  if  an  increase  in  the  inflamma- 
tion and  effusion  should  occur,  aspiration  may  be  repeated,  depending  on  the 
nature  of  the  fluid  as  to  the  future  course  of  procedure.  It  is  not  frequent, 
however,  that  any  further  difficulty  is  encountered.  The  temperature  and 
pain  usually  subside  within  a  few  days,  and  the  joint  gradually  resumes  a 
normal  condition. 

POSTOPERATIVE   -MEASURES. 

The  limb  is  maintained  in  a  position  of  physiologic  rest  until  the  wound 
is  entirely  healed  and  all   signs   of   inflammation   have   disappeared.     The 


RAXSOHOfF  MEMORIAL  VOLUME 


patient  is  then  given  the  privilege  of  active  motion  once  or  twice  a  day, 
depending  on  the  sense  of  pain  as  a  guide  to  the  extent  of  movement.  Later, 
gentle  passive  motion,  along  with  heat  and  massage,  will  often  hasten  recov- 
ery, but  at  first  the  utmost  gentleness  is  necessary  in  order  to  minimize  the 
risk  of  exciting  a  recrudescence.  The  absence  of  signs  of  inflammation  does 
not  always  assure  the  absence  of  pathogenic  organisms,  and  well  meant 
efforts  to  establish  mobility  may  set  up  an  active  condition  within  the  joint, 
if  passive  motion  is  applied  too  vigorously  or  begun  too  soon. 

Should  fibrous  adhesions  form,  which  we  feel  reasonably  sure  are  peri- 
articular, they  may  be  broken  down  by  forced  manipulations,  with  the  patient 
under  full  anesthesia,  in  order  to  secure  complete  muscular  relaxation,  thus 
permitting  the  movements  to  be  carried  sufficiently  far  in  all  directions. 

Intra-articular  adhesions  are  best  treated  by  gradual  correction  by  means 
of  suitable  mechanical  appliance,  since  rough  handling  is  followed  by  further 
damage  to  the  joint  structures  and  still  greater  limitation  of  movement  within 
the  articulation. 


THE  MECHANISM  OF  SHOCK  AND  EXHAUSTION.* 

By  Gkokc.e  W.  Crilk.  M.  D.,  F.  A.  C.  S. 

Cleveland. 

The  man  in  acute  shock  or  exhaustion  is  able  to  see  danger,  but  lacks 
the  normal  muscular  power  to  escape  from  it ;  his  temperature  may  be  sub- 
normal, but  he  lacks  the  normal  power  to  create  heat ;  he  understands  words, 
but  lacks  the  normal  power  of  response.  In  other  words,  he  is  unable  to 
transform  potential  into  kinetic  energy  in  the  form  of  heat,  motion,  and 
mental  action,  despite  the  fact  that  his  vital  organs  are  anatomically  intact. 
His  mental  power  fades  to  unconsciousness ;  his  ability  to  create  body  heat 
is  diminished  until  he  approaches  the  state  of  the  cold-blooded  animal ;  the 
weakness  of  the  voluntary  muscles  finally  approaches  that  of  sleep  or  anes- 
thesia ;  the  blood-pressure  falls  to  zero ;  most  of  the  organs  and  tissues  of  the 
body  lose  their  function. 

It  is  evident,  therefore,  that  in  exhaustion  the  organism  has  lost  its  self- 
mastery.  Self-mastery  is  achieved  only  by  the  normal  action  of  tlie  master 
tissue — the  brain.  In  exhaustion,  then,  is  the  brain  primarily  exhausted;  or 
has  some  other  tissue  or  organ  functionally  broken  down,  and  has  that 
breakdown  carried  with  it  exhaustion  of  the  brain?  If  the  latter,  then  what 
organs  and  tissues  are  vitally  necessary  to  the  brain  for  the  performance  of 
its  function?  Obviously,  the  exhaustion  of  any  organ  or  tissue  not  vital  to 
the  performance  of  brain  function  need  not  be  considered,  since  it  probably 
would  not  be  a  direct  cause  of  acute  exhaustion. 

I.  TISSUES  AND  ORGANS  WHICH  BEAR  NO  IMMEDIATE  RELATION  TO 
THE  PROBLEM  OF  ACUTE  EXHAUSTION. 
Among  the  tissues  and  organs  that  are  not  immediately  vital  to  the  brain, 
within  the  period  of  death  from  acute  exhaustion,  are  the  bones  and  joints, 
the  connective  tissue,  the  neutral  fats,  the  skin,  the  genito-urinary  system, 
the  digestive  system,  the  gall-bladder  and  ducts,  the  lymphatic  vessels  and 
glands,  the  salivary  glands,  the  spleen,  the  sweat  glands,  the  pancreas,  the 
thyroid,  the  thymus,  the  organs  of  common  sensation,  the  nails,  the  hair. 
Want  of  activity  of  any  of  these  organs  or  tissues  individually  or  collec- 
tively cannot  produce  acute  exhaustion  in  the  sense  in  which  that  word  is 
here  used.  That  is  to  say,  a  man  in  exhaustion  from  the  injury  and  the 
struggle  of  battle  would  not  be  restored  if  he  were  given  rested  eyes,  rested 
ears,  rested  sweat  glands,  rested  spleen,  rested  genito-urinary  system, 
rested  digestive  system,  rested  bones  and  joints,  rested  connective  tissue, 
rested  skin,  rested  gall-bladder,  rested  fat. 

II.    TISSUES  AND  ORG.^TCS  WHOSE  FAILURE  OF  FUNCTION  MAY 

PRODUCE  ACUTE  EXHAUSTION. 
The   tissues   and   organs,   whose   failure   of    function   may   cause   acute 
exhaustion,  are  the  respiratory  system,  the  circulatory  system,  the  blood,  the 
muscles,  the  adrenals,  the  liver,  and  the  brain. 

•From  Journal  A.  M.  A.,  November  23.   1920. 

Page  7.T 


RAXSOHOPf'  .MEMORIAL  VOLUME 


Respiuatory  System. 

RELATION  OF  THE  RESPIRATORY  SYSTEM   TO  SHOCK  AXD 
EXHAUSTION. 

The  failure  of  the  respiratory  system  to  deliver  sufficient  oxygen  to  the 
Ijlood  or  to  take  sufficient  CO,  from  the  blood,  exhausts  and  kills  promptly. 
Failure  of  the  respiratory  system  is  not  a  universal,  not  even  a  common 
cause  of  exhaustion,  for  in  the  great  majority  of  cases  of  exhaustion,  the 
respiratory  activity  is  even  increased  and  there  is  no  interference  in  the 
lungs  with  the  exchange  of  gases.  The  interference  with  the  pulmonary 
mechanism  of  air  exchange  that  may  cause  exhaustion  is  most  commonly 
produced  by  edema  of  the  alveolar  walls ;  by  pulmonary  embolism ;  by  the 
exudations  of  pneumonia ;  by  fat  embolism ;  by  the  inhalation  of  water,  or 
of  pus,  or  of  free  blood;  by  excessive  pleural  effusion;  by  emphysema;  by 
hemo-  and  pneumo-thorax.  In  each  of  these  conditions,  there  is  interfer- 
ence with  the  intake  of  oxygen  and  the  elimination  of  carbon  dioxid  which 
may  be  suflicient  to  cause  exhaustion  and  death. 

THEORIES  REGARDING  THE  RELATION  OF  THE  RESIMR ATORY 
SYSTEM  TO  SHOCK  AND  EXHAUSTION. 

Fat  Eiiibolisin  Theory.  Roswell  Park  first  suggested  and  Bissel  demon- 
strated the  presence  of  fat  embolism  in  the  lungs  of  ])atients  who  were 
diagnosed  as  being  in  surgical  shock.  Porter  has  extended  Bissel's  obser- 
vations into  an  inclusive  theory  of  shock.  He  concludes  that  shock  is  due 
mainly  to  diffuse  fatty  embolism  of  the  lungs.  There  are  several  facts  that 
apparently  are  not  harmonized  by  the  fat  embolism  theory. 

(a)  In  cases  of  abdominal  penetration,  if  there  is  no  perforation  of 
the  hollow  viscera  and  no  hemorrhage,  there  is  little  shock;  if  there  is 
either  perforation  or  hemorrhage,  or  both,  there  is  shock.  Since,  in  either 
case,  the  same  fat  areas  have  been  traversed,  it  follows  that  the  traversing 
of  the  fat  was  not  the  determining  factor. 

(b)  In  emotional  shock,  so  common  in  battle,  it  is  difficult  to  assign  to 
fat  emboli  a  causative  role. 

(c)  In  shock  from  burns,  the  difficulty  is  no  less. 

(d)  In  shock  from  chest  and  head  injuries,  i!  is  almost  as  difficult  to 
as.sign  a  causative  role  to  fat  emboli.    Many  other  examples  may  be  cited. 

On  the  other  hand,  surgical  literature  contains  many  accounts  of  the 
presence  of  fat  emboli  in  fracture  cases — especially  fractures  of  the  long 
bones,  and  these  cases  show  no  shock  at  first,  hut  later  develop  a  train  of 
symptoms  resembling  shock. 

Wiggers  performed  a  series  of  experiments  to  determine  whether  the 
mechanism  which  causes  failure  of  the  circulation  after  the  intravenous 
injection  of  oil  is  the  same  as  that  which  causes  circulatory  failure  in  surg- 
ical shock.  He  concluded  that  circulatory  failure  produced  by  fat  emboli 
must  be  distinguished  from  circulatory  failure  due  to  surgical  shock.     The 


GEORGE  W.  CRILE 


conclusions  of  Wiggers  are  in  more  complete  accord  with  surgical  experi- 
ence than  those  of  Porter.  ^Vith  respect  to  the  CO,  treatment  which  Porter 
proposes,  on  the  theory  that  (he  increased  action  of  the  diaphragm  caused 
by  the  CH^  would  force  the  fat  emboli  out  of  the  capillaries  into  the  free 
circulation,  it  would  obviously  be  difficult  to  determine  how  nuicli  nf  (he 
clinical  result  might  be  due  to  pooling  of  the  blood  in  the  abrlominal  \cins, 
for  which  Porter  advises  CO,  inhalation,  and  how  much  to  pulmonary  fat 
embolism  for  which  also  he  advises  CO,  inhalation.  That  is,  would  the 
clinical  result  be  due  to  the  pumping  of  the  blood  out  of  the  abdominal  ves- 
sels by  the  increased  respiration  induced  by  the  inhalation  of  CO^,  or  to  the 
driving  of  the  fat  out  of  the  lungs,  or  would  it  be  due  to  the  relief  of  acapnia 
(Henderson)  ?  But  since  in  practice  the  CO,  treatment  has  yielded  no 
advantage  to  the  patient,  this  point  will  not  l)e  [Jursued  further. 

Henderson's  Acaj^nia  Theory,  ^'andell  Henderson  has  plausibly  advo- 
cated the  view  that  excessive  ventilation  of  the  lungs — resulting  in  excessive 
elimination  of  CO,  from  the  blood — is  the  cause  of  shock.  Since  the  respira- 
tory center  is  controlled  largely  by  the  CO,  tension  of  the  blood,  it  follows 
that  in  shock  the  respiratory  exchange  would  be  diminished,  so  that,  as 
Henderson  believes,  there  would  result  a  state  which  is  below  the  jjoint  of 
oxygen  safety, 

Henderson's  theory  is  one  which  every  surgeon  wf)uld  hope  might  be 
true,  for  apparently  it  would  make  both  the  prevention  and  the  cure  of  shock 
easy  and  simple.  There  are  many  arguments  in  favor  of  this  theory.  The 
disturbing  efifect  of  excessive  ventilation  of  the  lungs  is  apparent.  It  is  true 
that  oxygen  improves  the  condition  of  the  patient  in  shock,  that  lack  of 
oxygen  leads  to  acidosis.  Nevertheless  there  are  certain  difticulties  in  the 
way  of  accejJting  fully  Henderson's  conclusions. 

(a)  As  we  have  stated  above,  the  clinical  use  of  CO,  in  shock  has  not 
proven  to  be  of  much  value.  It  is  possible  that  this  is  because  .serious  intra- 
cellular damage  has  been  inflicted  upon  certain  vital  organs  before  the  CO, 
treatment  was  begun. 

(b)  In  my  laboratory,  animals  under  curare  and  continuous  ade(|uate 
and  even  artificial  respiration — thus  eliminating  the  excessive  ventilation 
(acapnia)  factor — could  still  be  killed  by  shock  from  trauma. 

•(c)  Protracted  consciousness — insomnia — in  animals,  subjected  lo  no 
other  excitement,  causes  complete  exhaustion.  Acapnia  could  scarcely  be 
a  factor  here.  It  should  l)e  added  that  Henderson  has  not  discussed  this 
type  of  exhaustion. 

CONCLUSION. 

In  exhaustion  from  running,  from  fevers,  from  trauma,  from  anesthesia, 
from  excision  of  the  liver,  from  excision  of  the  adrenals,  from  hemorrhage, 
from  emotion,  from  insomnia,  the  exhaustion  is  not  in  any  way  related  to 
the  lungs.  If  there  is  a  coexistent  defect  in  ihc  pulmonary  function,  by  so 
much  the  more  readily  is  exhaustion  produced  by  trauma;  by  emotion,  by 


RANSOHOFF  MFMORIAL  VOLUME 


fever,  by  exertion,  liy  hemorrhage,  etc.  We.  therefore,  conclude  that  the 
Iirimary  cause  of  exhaustion  may  be  found  in  the  pnUnoiiary  system,  but  that 
this  is  not  a  coiiiiiioii  primary  cause. 

Circulatory  System. 
I'aihn-e  of  the  circulation  exhausts  and  kills  inevitably,  and  failure  of  the 
circulation  is  established  sooner  or  later  in  acute  cases  of  grave  or  fatal 
exhaustion.  The  question  therefore  is :  Is  the  failure  of  the  circulation 
a  primary  or  a  secondary  cause  of  exhaustion,  or  is  the  circulatory  factor 
sometimes  a  primary  and  sometimes  a  secondary  cause  of  exhaustion? 

THK  HE.\RT. 
The  heart  may  be  unable  to  pump  the  blood  stream  forcibly  enough  to 
maintain  adequate  circulation,  in  which  case  general  exhaustion  will  occur 
as  the  result  of  lack  of  oxidation  of  the  tissues.  Exhaustion  occurs  clin- 
ically in  the  myocarditis  of  acute  or  prolonged  infections;  as  the  result  of 
excessive  muscular  exertion;  in  anemia;  in  the  presence  of  valvular  defects, 
r.ut  observations  in  both  the  clinic  and  the  laboratory  show  that  in  surgical 
shock  and  exhaustion,  the  heart  muscle  has  not  failed. 

DISTRIBUTION  OF  BLOOD. 
Pooling  in  the  larger  veins.    A  number  of  observers  have  held  the  view 
I  hat  in  shock  the  blood  accumulates  in  various  blood-vessels,  this  pooling 
becoming  in  effect  an  intravascular  hemorrhage.     There  are  certain   facts, 
however,  which  arc  not  harmonized  by  this  theory. 

(a)  In  the  author's  laboratory,  experiments  showed  that  shock  could 
be  produced  in  animals  in  which  the  abdominal  vessels  or  the  thoracic  aorta 
had  been  excluded  by  ligation,  though  not  quite  as  readily  as  in  the  controls. 
Erlanger  and  others  have  shown  that  excision  of  all  the  abdominal  viscera 
does  not  lessen  the  liability  to  shock.  In  our  experiments  we  found  al.so 
that  if  the  intestines  were  so  tensely  distended  with  water  as  to  drive  out  all 
the  blood,  then  trauma  of  the  peritoneum  no  longer  caused  a  primary  fall  in 
blood-pressure,  but  death  from  shock  might  occur.  Many  dissections  before 
death,  many  autopsies  after  death  from  trauma  to  other  parts  of  the  body 
than  the  abdomen,  showed  that  tlie  blood  was  held  in  the  veins  everywhere, 
as  in  death  from  other  causes. 

(b)  As  stated  in  a  preceding  paragraph.  Porter  has  proposed  the  inha- 
lation of  CO2  for  the  purpose  of  increasing  activity  of  the  diaphragm,  to 
the  end  that  the  supposed  accumulation  of  blood  in  the  abdomen  would  thus 
be  put  into  more  active  circulation.  No  clinical  advantage  from  this  treat- 
ment has  been  reported. 

(c)  Treatment  with  intraperitoneal  injections  of  pituitrin.  as  sug- 
gested by  Cannon,  even  more  effectively  facilitates  the  splanchnic  venous 
circulation  than  does  Porter's  CC\,  inhal;itinn,  but  this  method  has  not  proved 
to  be  a  cure  for  shock. 


GEORGE  ]V.  CHILE 


From  the  evidence  in  hand,  we  are  not  warranted  in  concluding  either 
that  blood  does  or  that  it  does  not  pool.  We  only  infer  that  even  if  it  does 
pool,  this  is  an  end  effect — not  a  primary  cause  of  shock. 

Accumulation  of  the  Blood  in  the  Catyillaries.  Cannon  has  advanced 
strong  arguments  in  favor  of  the  view  tliat  the  small  blood-vessels — the 
capillaries — are  dilated,  and  in  dilating  have  engulfed  so  much  of  the  volume 
of  the  blood  as  to  seriously  interfere  with  the  circulation.  If  this  were 
true,  then  the  universal  bandaging  of  the  body  alone,  or  blood  transfusion 
alone,  or  bandaging  and  blood  transfusion  combined,  should  both  prevent 
and  cure  shock.  But  both  laboratory  and  clinical  experience  show  that. 
although  these  measures  are  useful,  they  are  not  specific. 

VASO-MOTOR   MECH.AXISM. 

Is  the  vaso-motor  mechanism  a  factor  in  shock?  In  1897  the  theory  that 
shock  was  due  to  the  impairment  or  breakdown  of  the  vaso-motor  mechan- 
ism was  proposed  by  the  writer.  Owing  to  the  fact  that  control  of  the 
blood-pressure  did  not  specifically  cure  shock  it  soon  became  obvious  that 
exhaustion  and  shock  included  much  in  addition  to  the  failure  of  the  vaso- 
motor mechanism. 

Opposing  views  as  to  the  state  of  the  vaso-motor  mechanism  have  been 
presented  by  various  investigators. 

(a)  Seelig  and  Lyon  have  concluded  that  the  vaso-motor  mechanism  is 
functionally  intact  in  shock. 

(b)  Porter  has  found  that  vaso-motor  stimulation  jiroduces  a  ])ro- 
gressively  diminished  rise  in  blood-pressure  as  shock  deepens.  This  finding 
is  in  accord  with  our  own  data.  Porter  has  interpreted  the  blood-pressure 
change  on  the  basis  of  a  percentile  rise,  and  has  concluded  that  the  vaso- 
motor mechanism  is  not  altered  in  shock.  It  is  open  to  question,  however, 
whether  Porter  has  not  proved  the  opposite  of  his  conclusions,  for  if,  in 
shock,  adrenalin  be  given  intravenously,  or  pressure  on  a  paw  be  made,  the 
percentile  rise  interpretation  will  be  reversed.  Applying  Porter's  percentile 
interpretation  to  the  effect  of  adrenalin  the  percentile  rise  would  be  over 
300  per  cent.,  that  is,  according  to  Porter's  reasoning,  the  vascular  state  is 
three  times  better  than  normal,  but  nevertheless,  the  dog  is  dying.  The 
error  in  Porter's  reasoning  may  be  made  more  clear  by  a  homely  illustra- 
tion. If  a  goad  be  applied  to  a  fresh  horse,  the  resulting  increase  in  speed 
may  be  stated  as  a  percentile  increase.  When  the  horse  is  in  extreme  fatigue 
and  an  equal  goad  is  applied,  the  percentile  increase  will  probably  be  the 
same,  but  nevertheless  the  horse  is  exhausted. 

(c)  Erlanger  and  his  associates  found  that  the  vaso-motor  mechanism 
is  exhausted  late  in  shock.  They  suggest  that  the  primary  fall  in  blood- 
pressure  may  be  brought  about  by  the  effect  of  painful  stimuli  and  hemor- 
rhage. 

(d)  Pike  and  Coombs  beliexc  that  damages  to  the  brain-cells  must  be 
included  as  one  of  the  conditions  of  traumatic  shock. 


RAXSOHOFF  MEMORIAL  VOLUME 


(c)  W'iggers  observed  a  steady  fall  in  xaso-niotor  tone  in  llie  early 
phases  of  shock.  He  concluded  that  the  ])eri|iheral  resistance  \vas  dimin- 
ished, indicating  diminished  vaso-motor  tone. 

Our  experimental  data  show  that  there  is  no  practical  distinction  to  be 
made  between  external  stimulation  of  the  vaso-niotor  center  as  in  injury  and 
operation,  and  internal  stimulation  by  vaso-motor  stimulants,  as  strychnin. 
Each  in  sufficient  amount  produces  exhaustion  (shock),  and  each  with  logic 
might  he  used  to  treat  the  shock  produced  by  the  other,  ^\'e  conclude, 
therefore,  that  in  traumatic  shock  the  vaso-motor  mechanism  is  function- 
ally impaired  or  exhausted. 

Experience  in  the  clinic,  however,  seems  to  show  that,  whereas  in  shock 
the  depression  and  fatigue  of  the  vaso-motor  centers  were  very  important, 
there  must  also  be  other  important  effects.  This  was  all  the  more  probable 
because  of  the  time  required  for  recovery;  the  long  after-effects;  the  inade- 
(|uacy  of  merely  raising  the  blood-pressure;  the  weakness  antl  debility  of 
the  injured  animal  before  a  fall  in  blood-pressure  had  occurred  ;  the  facts 
that  infection,  loss  of  sleep,  hunger  and  thirst  predisposed  to  exhaustion 
and  that  ether  anesthesia  predisposed  to  exhaustion.  All  these  clinical  obser- 
vations demanded  renewed  research.  The  work  of  Hodge  on  fatigue  in 
bees  and  birds  suggested  such  an  investigation.  To  that  end  the  studies  of 
the  brain  cells,  which  have  been  summarized  in  former  publications,  were 
undertaken.  These  studies  immediately  gave  us  illuminating  results.  Our 
argument  was  that  if  the  \aso-motor  center  was  fatigued  in  shock  and 
exhaustion,  other  parts  of  the  brain  were  probably  fatigued  also.  If  the 
brain  cells  were  fimctionally  altered,  one  would  expect  them  to  be  phys- 
ically altered,  as  Hodge  had  shown  was  the  ca.se  in  his  studies  of  fatigue  in 
the  bee.  \\'e  argued  that  in  shock  not  only  are  the  vaso-motor  cells  ex- 
hausted, but  the  cells  of  the  brain  that  ])reside  over  voluntary  muscular 
action  and  mental  action  are  also  altered ;  in  other  words,  that  the  brain  as  a 
whole  is  altered,  and  is  altered  independently  of,  as  well  as  in  consequence 
of,  the  low  blood-pressure  di>e  to  the  exhaustion  of  the  vaso-motor  cen- 
ters ;  that  the  higher  centers  may  well  be  affected  even  more  than  the  vaso- 
motor 

The  vaso-motor  niechanisni  alone,  the  blood-pressure  alone,  is  not  suf- 
ficient to  account  for  all  the  phenomena  of  shock  ;  and  although  some  of 
the  causes  of  exhaustion  may  be  found  in  the  resjjiratory  system,  and  some 
in  the  circulatory  system,  we  must  look  elsewhere  for  the  explanation  of  the 
vast  majority  of  ca.ses  of  shock  and  exhaustion.  Are  these  due  to  some 
change  in  the  blood? 

THE  BLCXJn. 

Chemical  Cliaiujcs  in  the  Hlood.  The  blood  is  a  vital  fluid  for  all  the 
tissues.  If  there  is  insuhicii  iit  bidod.  or  if  ihc  l)l()od  is  sullicienlly  impure, 
exhaustion  of  e\ery  organ  and  lissu.e  will  fulldw.  The  acute  exhaustion 
caused  by  hemorrhage  is  cured  in  a  normal  animal  by  immediate  replace- 
Pagc  so 


GEORGE  IV.  CRJLE 


ment  of  the  lost  blood  by  an  equal  amount  of  good  blood  from  another 
animal.  If  impure  blood  is  the  primary  cause  of  exhaustion,  and  no  other 
jirimary  cause  exists,  then  the  removal  of  impure  blood  and  the  substitution 
of  pure  blood  should  bring  relief  from  exhaustion  in  proportion  to  tlie 
amount  of  impure  blood  exchanged  for  pure  blood.  If  exhaustion  is  due  to 
some  change  in  the  blood,  then  if  an  acutely  exhausted  animal  had  its  blood 
withdrawn  as  completely  as  possible  and  normal  blood  replaced,  the  same 
process  being  repeated  several  times  so  as  to  be  certain  that  a  sufticient 
amount  of  blood  had  been  exchanged,  demonstrable  relief  should  follow. 
But  experiments  have  shown  that  not  many  cases  of  exhaustion  may  thus 
be  benefited  or  cured.  Moreover,  animals  exhausted  by  insomnia  show  no 
change  in  the  blood  picture,  as  has  been  shown  by  our  experiments.  \\'e 
have  found,  also,  that  in  patients  in  whom  exhaustion  has  developed  grad- 
ually, there  may  be  no  change  in  the  blood. 

The  common  pathologic  change  in  the  blood  in  acute  exhaustion  is  acido- 
sis. If  this  were  the  primary  cause  of  exhaustion,  then  infusion  of  sodium 
bicarbonate  should  prevent  and  cure ;  but  both  laboratory  and  clinical  evi- 
dence shows  that  alkalies  neither  prevent  nor  cure  shock. 

Cannon  has  found  decreased  reserve  alkalinity  in  wounded  soldiers  in 
shock.  He  found  this  decrease  was  more  marked  in  operation  under  ether 
than  in  ojierations  under  nitrous  oxid;  he  believes  that  a  diastolic  blood- 
pressure  of  about  80  is  a  critical  level  at  which  acidosis  rapidly  develops. 
These  phenomena  are  obviously  secondary  causes  of  exhaustion. 

Cannon,  Dale  and  Bayliss  have  recently  found  that  the  pulpefaction  of 
muscles  causes  a  fall  in  blood-pressure  when  the  nerve  sup])ly  of  the  injured 
part  in  blocked ;  and  that  this  is  prevented  when  the  circulation  of  the  part 
is  blocked.  Even  so.  macerated  muscle  products  could  be  but  a  minor  factor 
in  the  production  of  shock,  for  (a)  tourniquets  minimize  shock  only  as  far 
as  they  minimize  hemorrhage;  (b)  spinal  and  local  anesthesia  almost 
specifically  prevent  shock;  (c)  many  causes  of  shock,  such  as  abdominal 
operations,  joint  injuries,  skin  injuries,  etc.,  have  no  relation  to  muscle 
poison;  (d)  nitrous  oxid  anesthesia  is  all  but  a  preventive  of  shock.  How 
can  these  facts  be  reconciled  with  the  view  that  the  cause  of  shock  is  low 
blood-pressure,  the  low  blood-pressure  in  turn  being  caused  by  muscle  poi- 
sons? Even  if  under  exceptional  circumstances  the  presence  of  muscle 
toxins  constituted  a  causative  factor,  their  shock-producing  value  would  be 
identical  with  that  of  toxemia  from  any  other  cause. 

Concentration  of  the  Blood.  The  blood  \oIume  is  apparently  dimin- 
ished in  shock.  Has  the  plasma  left  the  vessels  and  gone  into  the  tissues? 
If  so,  is  the  process  an  adaptation  or  is  it  a  pathologic  effect?  This  point 
was  investigated  in  our  laboratory  Ijy  Drs.  F.  W.  Hitchings,  A.  N.  Eisen- 
brey,  and  C.  H.  Lenhart,  who  found  that  in  shock  the  concentration  of  the 
blood  was  increased  up  to  20  per  cent.,  but  other  considerations  made  it 
obvious  that  this  is  not  a  primary  cause  of  shock. 


RAXSOHOFF  MEMORIAL  VOLUME 


"In  the  blood  of  the  'shock  dogs'  there  was  an  increase  in  the  nnniber  of 
the  red  cells  per  cubic  millimetre  while  in  the  blood  of  the  'hemorrhage  dogs' 
there  was  a  decrease  in  the  nnmber  of  red  cells  per  cubic  millimetre. 

"In  the  'shock  dogs'  there  was  a  decrease  in  the  number  of  white  cor- 
l)uscles  while  in  the  'hemorrhage  dogs'  there  was  a  preliminary  decrease 
followed  by  a  marked  increase."* 

Mann  performed  a  more  extensive  research  along  the  same  line,  and 
attributed  greater  importance  to  the  increased  concentration.  Cannon  has 
shown  further  evidence  of  loss  of  plasma  in  shock,  and  supports  Mann's 
estimation  of  the  value  of  this  data  rather  than  our  own.  Now,  if  increased 
concentration  were  the  cause  of  the  small  amount  of  blood,  if  circulatory 
failure  were  due  to  a  'plasma  hemorrhage'  into  the  tissues,  then  adequate 
transfusion  of  blood  should  prevent  and  cure  shock,  but  adequate  transfu- 
sion of  blood  is  not  a  specific  cure.  In  addition,  on  this  theory,  the  careful 
work  of  Hogan  and  Bayliss  on  the  infusion  of  colloidal  solutions,  should 
have  given  us  a  cure,  because  it  is  known  that  these  solutions  do  not  leave 
the  blood  stream.  But  colloidal  solutions  fail  to  hold  the  blood-pressure — 
fail  to  cure  advanced  cases.  The  transference  of  plasma  is  probably  an 
adaptive  protection. 

Then,  again,  even  granting  that  the  blood  contains  impurities  which 
cause  exhaustion,  where  did  the  blood  get  those  impurities?  From  the  cells. 
And  the  cells?  From  their  increased  metabolism,  ^^'hat  caused  that  in- 
creased metabolism?  Certain  of  the  excitants  of  exhaustion.  We  conclude, 
therefore,  that  in  the  absence  of  primary  disease — causing  changes  in  the 
blood,  and  in  the  absence  of  hemorrhage,  changes  in  the  blood  or  in  the 
blood-pressure  are  a  secondary,  not  a  primary  cause  of  exhau.stion. 

VOLUXT.XRY   .MUSCLES. 

If  the  voluntary  system  were  exhausted  primarily  in  shock,  then  there 
would  be  prostration,  low  temperature,  lowered  blood-pressure,  but  not  the 
extremely  low  blood-pressure  often  seen  in  shock,  no  sweating,  no  loss  of 
mental  symptoms.  Therefore,  it  at  once  becomes  apparent  that  primary 
exhaustion  of  the  voluntary  muscles  could  not  be  adequate  cause  of  all 
symptoms  of  exhaustion. 

Is  exhaustion  of  the  voluntary  muscles  the  cause  of  the  lowered  body 
temperature?  Is  the  inability  of  the  muscles  to  act  due  to  a  primary  change 
in  the  muscles,  while  the  brain  is  normal?  This  seems  improbable,  for  the 
following  reasons ; 

(a)  The  voluntary  muscle  is  more  resistant — more  than  fifty  times  as 
resistant — to  low  blood-pressure  and  anemia  as  the  brain.     (Crile-Dolley.) 

(b)  The  muscles  in  the  acutely  exhausted  subject  show  no  histological 


GEORGE  W.  CRILE 


change.    The)-  can  be  made  to  contract  by  electric  stimulation  of  their  nerve 
supply,  or  by  electric  stimulation  of  the  muscle  directly. 

(c)  It  i.s  a  physiologic  axiom  that  voluntary  nuiscles  are  not  as  readily 
exhausted  as  are  the  nerve  centers  that  govern  them. 

(d)  If  there  is  primary  exhaustion  of  the  muscles,  then,  according  to 
Bayliss,  it  would  probably  be  due  to  the  over-production  of  acid  or  other 
injuring  by-products  as  a  result  of  injury  or  of  work  performed.  But  in 
exhaustion  from  trauma  under  anesthesia,  the  muscles  have  done  no  work ; 
in  exhaustion  from  fear,  the  muscles  have  done  little  work ;  in  exhaustion 
from  overwhelming  toxemia,  there  has  been  no  muscular  work.  Finally, 
we  know  that  in  a  \ast  number  of  the  injuries  which  cause  shock,  no  muscle 
is  involved,  c.  g..  injury  of  the  skin,  brain,  knee-joint,  hands  or  feet  may 
result  in  .shock. 

We  must,  therefore,  conclude  that  the  voluniarv  nuiscular  system  plays 
a  secondary,  not  a  primary  role  in  exhausticm.  We  ha\c  seen  that  the 
respiratory  and  the  circulatory  systems  and  the  \oluntary  muscular  system 
are  sometimes  primary  causes  of  exhaustion,  and  frequently  secondary 
causes.  We  have  seen  that  in  exhaustion  all  these  tissues  sut+'er  a  variable 
amount  of  disability,  but  the  primary  common  cause  of  shock  remains  to 
be  disclosed. 

THE  .\nRE.\.\LS. 
The  criteria  for  the  objective  study  of  the  adrenals  are  the  adrenalin 
output,  the  electric  conductivity,  and  the  histologic  picture.  Elliott.  Cannon. 
and  others  have  found  an  increased  adrenalin  output  and  a  diminished  adre- 
nalin content  in  certain  cases  of  exhaustion,  c.  g..  in  exhaustion  due  to 
inhalation  anesthesia,  to  infections,  and  to  emotion.  Short  found  no  notable 
diminution  in  the  adrenalin  content  in  shock;  Bedford  found  no  diminution 
of  adrenalin  output  in  shock ;  Mann  disassociates  the  adrenals  from  shock. 
In  our  laboratory  we  found  cytologic  changes  in  the  adrenals  in  exhaustion 
from  any  cause,  including  insomnia,  these  changes  being  more  marked  in 
the  cortex  than  in  the  medulla. 

THE  RELATION  OF  THE  ADREN.ALS  TO  THE  LUER  .\XD  TO  THE 
RRAIX  IX  EXHAUSTIOX. 

Apparently  adrenalin  alone  can  cause  the  brain  to  greatly  increase  its 
work.  By  cross-circulation  experiments,  we  have  found  that  adrenalin  causes 
increased  activity  of  the  central  vaso-motor  mechanism.  Not  only  can  adre- 
nalin, as  Cannon  has  shown,  cause  all  the  basic  phenomena  of  exertion, 
emotion,  infection,  etc.,  but  it  also  causes  brain-cell  lesions  identical  with 
those  produced  by  exertion,  emotion,  infection,  etc.,  including  the  entire 
cycle  of  hyperchromatism,  chromatolysis,  swelling  and  even  disintegration 
of  the  brain  cells.  'Plie  injecti(jn  of  adrcn.-ilin  causes  an  immediate  increase 
in  the  conductivity  <if  the  br.ain  to  alxixc  the  normal,  followed  1)\-  a  later 
decrease   to  below   the   normal;   moreoxur.   adrenalin   causes   an    immediate 


RAXSOHOfF  MEMORIAL  f  GLUME 


increase  in  the  temperature  of  the  brain,  as  evidenced  by  thermo-couple 
measurements,  ^^'e  know  that  when  the  adrenals  are  excised,  the  brain- 
cells  undergo  a  progressive  cytolysis ;  and  there  is  no  primary  stage  of  hyper- 
chroniatism,  but  an  immediate  and  progressive  chromatolysis,  edema,  and 
final  breakdown. 

From  these  facts  it  would  apjiear  that  the  brain  is  profoundly,  even 
vitally,  dependent  upon  the  adrenals  ;  that  without  the  adrenals,  the  brain 
rapidly  loses  not  only  its  functional  power,  but  also  its  power  of  survival. 
How  is  the  influence  of  the  adrenals  upon  the  brain  exerted?  Is  it  the  result 
of  the  direct  action  of  adrenalin  on  the  brain-cells?  Does  adrenalin  owe  its 
effect  upon  the  brain-cells  to  the  resultant  formation  of  an  increased  amount 
of  oxyhemoglobin  in  the  lungs,  which  was  demonstrated  by  Dr.  Menten ; 
or  to  its  power  of  increasing  the  alkalinity  of  the  blood?  Or  does  adre- 
nalin owe  its  remarkable  eflfect  on  the  brain-cells  to  an  intermediate  efifect 
on  some  other  organ,  such  as  the  thyroid  (Aschoiif,  Cannon),  or  the  liver? 

That  the  adrenals  exert  also  a  vital  influence  on  the  liver  has  been 
demonstrated  by  the  cytologic  changes  produced  by  the  intravenous  injection 
of  excessive  amounts  of  adrenalin — chromatolysis,  edema,  displacement  of 
nuclei,  loss  of  the  power  of  diflferential  staining.  Similar  cytologic  changes 
in  the  liver  cells  follow  double  adrenalectomy.  When  the  liver  cells  are 
thus  altered,  from  whatever  cause,  the  brain  is  unable  to  do  its  work  nor- 
mally, and  becomes  exhausted.  Assuming  that  the  absence  or  the  excess 
of  adrenalin  causes  changes  in  the  cells  of  the  brain  and  the  liver  charac- 
teristic of  exhaustion,  then  does  adrenalin  produce  these  changes  in  the 
brain-cells  primarily  by  acting  directly  on  the  brain,  or  secondarily  by  first 
acting  on  the  liver?  It  is  known  that  adrenalin  facilitates  oxidation — hence 
it  facilitates  energy  transformation,  and  therefore,  the  internal  respiration 
of  the  cells  of  each  organ  would  be  speeded  up  by  the  presence  of  adrenalin 
and  diminished  by  its  absence.  The  brain,  being  dependent  on  the  func- 
tional integrity  of  the  liver,  and,  the  liver  being  dependent  in  part  on  the 
adrenals,  and  each  being  dependent  on  oxidation,  which  in  turn  is,  in 
part  at  least,  dependent  on  the  adrenals,  we  must  conclude  that  the  liver 
and  the  brain  are  not  only  dependent  on  each  other,  but  upon  the  adrenals 
as  well. 

We  may  conclude,  therefore,  that  the  adrenals  are  factors  in  the  pri- 
mary cycle  of  exhaustion,  though  their  role  cannot  be  accurately  defined. 
THK  LI\'EK. 

Is  the  primary  cause  of  exhaustion  to  be  found  in  the  liver?  That  the 
liver  is  necessary  to  the  functional  activity  of  the  brain  is  proved  by  the 
following  data : 

(a)  After  excision  of  the  liver,  the  power  of  the  brain  to  drive  the 
organism,  to  transform  potential  energy  into  kinetic  energy,  such  as  heat 
or  muscular  or  mental  action,  is  rapidly  diminished  and  completely  lost  at 
the  time  of  inevitable  death,  usually  within  a  few  hours. 


GEORGE  IV.  CRILE 


(b)  The  brain-cells  show  changes  in  their  cytologic  structure  which  are 
progressive  from  the  moment  their  liver  is  excised. 

(c)  After  excision  of  the  liver  the  temperature  of  the  brain  falls  pro- 
gressively until  death. 

(d)  In  every  type  of  exhaustion  from  whatever  cause,  the  cells  of  the 
liver  invariably  show  cytologic  changes,  such  as  diminished  power  of  dif- 
ferential staining,  edema,  and  eccentric  position  of  the  nucleus. 

(e)  Granting  adequate  circulation  and  respiration  in  a  decapitated 
animal,  the  excision  of  the  liver  causes  death  earlier  than  decapitation  or 
adrenalectomy. 

Some  of  the  most  important  functions  of  the  liver  remain  to  be  discov- 
ered, but  there  is  one  possible  relation  to  which  we  may  allude :  The  brain- 
cells  contain  almost  no  stored  carbohydrates  or  neutral  fats;  they  contain 
almost  no  factors  of  safety  against  acidosis.  They  have  almost  no  stored 
oxygen.  The  brain-cells  are  almost  wholly  dependent  on  the  blood  for 
oxygen  and  for  carbohj'drate  fuel  to  maintain  their  active  and  continuous 
metabolism;  the  blood  is  dependent  on  the  liver  for  sugar  for  the  brain. 
Apparently,  for  its  protection  against  want  of  sugar,  against  intra-cellular 
acidosis,  the  brain  is  in  part  dependent  on  a  long-distance  connection  with 
other  tissues,  especially  the  liver.  The  liver-cells  are  endowed  with  a  great 
facility  for  autolysis ;  the  brain-cells  are  but  slightly  subject  to  autolysis. 
We  may  suppose  that  the  keen,  stable  brain-cells  have  a  special  chemical 
dependence  on  the  remarkably  unstable  liver  cells.  For  opposite  reasons, 
then,  the  two  organs  that  are  most  suscejitible  to  acidosis  are  the  brain  and 
the  liver — the  brain  because  of  its  extreme  activity  in  acid  production  and 
because  of  its  lack  of  intracellular  defence  against  acidosis,  the  liver  because 
of  its  avidity  for  acids,  possibly  an  adaptation  for  the  protection  of  other 
vital  organs,  especially  the  brain.  If  the  brain-cells  contained  space  for  the 
storage  of  reserve  supplies  of  energy-producing  material  and  protection 
against  acidosis,  in  proportion  to  the  space  provided  for  this  purpose  in  the 
cells  of  other  organs,  not  only  would  the  size  of  the  brain  be  greatly  and 
awkwardly  increased,  but  its  power  to  do  work  would  be  correspondingly 
diminished. 

The  integrity  of  the  liver  is  essential  to  the  work  of  the  brain  ;  and  the 
integrity  of  the  liver  is  also  essential  to  the  elimination  of  the  acid  by- 
products of  metabolism  by  the  kidneys  and  the  lungs.  When  the  liver  is 
excised,  the  blood  tends  to  become  acid  as  the  animal  approaches  exhaustion. 
The  transfusion  of  blood,  the  administration  of  adrenalin  or  of  morphin 
exert  not  the  least  check  on  the  exhaustion  and  death  which  follow  excision 
of  the  liver.  On  the  other  hand,  decapitation  apparently  does  not  interfere 
with  the  function  of  the  liver. 

For  its  oxidizing  and  reducing  power,  the  liver  apparently  depends,  in 
part  at  least,  on  the  adrenals ;  for,  as  we  have  stated  above,  the  excessive 
intravenous  injection  of  adrenalin  on  the  one  hand,  and  adrenalectomy  on 

Page  85 


RAXSOHOfF  MEMORIAL  VOLUME 


the  other,  cause  marked  cytologic  changes  in  the  liver-cells — chromatolysis. 
edema,  eccentric  position  of  the  nucleus. 

In  our  electric  conductivity  studies  we  found  that  in  exhaustion  from 
any  cause  the  liver  and  the  brain  were  afifected  in  opposite  direction,  /.  c. 
in  extreme  exhaustion  the  conductivity  of  the  brain  was  decreased,  and  the 
conductivitv  of  the  liver  was  increased.  In  the  earliest  stages  of  stimula- 
tion, these  changes  were  reversed,  the  period  of  increased  conductivity  of 
the  brain  apparently  corresponding  to  the  period  of  hyperchromatism  estab- 
lished by  our  histological  studies. 

From  these  premises,  we  conclude  that  the  liver  is  inseijarably  associated 
with  the  brain  and  the  adrenals  in  the  production  of  shock  and  exhaustion ; 
but  as  the  liver  has  no  means  of  immediate  contact  with  the  external  excitants 
of  shock  and  exhaustion,  it  apparently  in  some  way  is  influenced  indirectly 
through  the  mediation  of  the  brain. 

\\'e  have  now  seen  that  c.rhaustion  may  be  produced  both  primarily  and 
secondarily  by  anatomical  and  functional  defects  and  disabilities  of  the 
respiratory  system,  of  tlie  circulatory  system,  of  the  blood,  of  the  liver,  of  the 
adrenals.  We  have  seen  that  in  exhaustion  these  organs  and  systems  share 
in  the  general  debility,  but  we  have  not  been  able  to  show  that  functional 
impairment  of  any  one  or  of  any  combination  of  these,  is  the  sole  cause  of 
the  exhaustion  of  the  organism  in  exertion,  in  emotion,  in  injury,  in  infec- 
tion, in  enforced  loss  of  sleep,  etc.  If,  then,  the  primary  cause  of  exhaus- 
tion is  not  disclosed  in  the  study  of  these  important  organs  and  tissues,  which 
are  either  directly  or  indirectly  driven  by  the  master  tissue,  the  brain  and 
the  nervous  tissue,  we  may  then  ask:  Is  the  primary  cause  of  exhaustion 
to  be  found  in  the  brain?  Has  the  brain  inherent  elements  of  weakness 
greater  than  those  of  any  other  organ  or  tissue  of  the  body? 

Thk:  Bk.mn  .\.\d  thic  Nervous  System. 
THE  BRAIX   .\S  AX   EXKRC.Y-TKAXSFORMIXG  OKGAX. 

Environment,  external  and  internal,  drives  the  brain;  and  the  brain 
either  directly  or  indirectly  drives  the  entire  organism.  Is  the  brain  tissue 
itself  a  transformer  of  potential  energy  into  kinetic  energy,  and  does  it 
drive  the  body  by  means  of  some  familiar  form  of  energy  which  it  creates, 
or  does  the  brain  drive  the  body  as  a  mystery  organ  obeying  no  physical 
laws?  Is  the  brain  capable  of  exhausting  itself  primarily  by  its  own 
excessive  work,  or  is  it  only  secondarily  exhausted? 

Do  the  brain-cells  transform  much  or  little  energy?  Are  they  active  or 
inactive  cells?  That  the  brain  transforms  potential  into  kinetic  energy,  and 
by  means  of  that  energy  drives  the  body,  is  shown  by  the  want  of  power  of 
action  when  the  head  is  cut  off.  That  the  brain  is  not  only  an  active,  but 
the  most  active  cnert/y-traiisforminy  organ  o-f  the  body,  is  held  by  Mathews. 

The  work  of  the  brain  is  greater  in  proportion  to  the  weight  of  its  tissue 
than  is  the  work  of  any  other  organ  of  the  body.  Alexander  and  Cserna 
state  that  the  i)rain  shows  a  consumption  of  O.i^O  cc.  of  0_.  ])er  gram  minute. 

Page  86' 


GEORGE  IV.  CRILE 


while  voluntary  muscle  showed  a  consumption  of  only  0.004  per  gram  min- 
ute. According  to  these  observers,  a  given  weight  of  brain  tissue  trans- 
forms energy  about  ninety  times  as  rapidly  as  an  equal  weight  of  the  volun- 
tary muscles  in  the  quiescent  state.  The  voluntary  muscles  constitute  42  per 
cent,  of  the  weight  of  the  body,  the  brain  2  and  3  per  cent.  Hence,  accord- 
ing to  the  findings  of  Alexander  and  Cserna,  excepting  when  active,  the 
brain  has  a  total  metabolism  five  times  greater  than  the  metabolism  of  all 
the  voluntary  muscles  together. 

From  these  facts,  we  conclude  that  the  brain  is  an  organ  of  intense  meta- 
bolism.    Are  the  brain-cells  safeguarded  against  the  factors  of  exhaustion? 

It  would  appear  that  the  brain-cell  is  evolved  stripped  to  its  decks,  to 
fight  the  battle  of  life;  as  if  its  function  as  an  energy-transformer  were 
so  important  that  certain  means  of  defence  are  withheld  from  the  brain-cell 
and  provided  for  it  by  other  organs,  e.  g.,  protection  against  intracellular 
acidosis,  against  want  of  oxygen,  against  want  of  food.  It  would  seem, 
therefore,  that  these  vital  functions  are  committed  to  other  organs.  The 
vast  volume  and  distribution  of  blood  in  the  liver,  in  the  lungs,  and  in  the 
kidneys  provide  for  the  rapid  elimination  of  waste  which  is  urgently  neces- 
sary, especially  for  the  safety  of  the  brain.  The  extreme  avidity  of  the 
liver  cells  for  acid  metabolites,  coupled  with  the  immense  cellular  surface 
exposed  to  the  blood  stream,  we  conceive  to  be  one  of  the  greatest  safe- 
guards to  the  brain  against  acidosis.  The  large  storehouse  of  sugar  in  the 
liver  serves  as  the  fuel  depot  for  the  brain  and  as  a  protection  against  want 
of  anaerobic  oxygen.  The  blood  stream  carried  oxygen  and  sugar  to  the 
brain ;  the  buiifer  substances  of  the  blood  are  a  continuous  protection  to  the 
brain  against  intracellular  acidosis.  The  brain-ccUs  iiiav  be  conceived  as 
liainng  their  protcctii'e  and  nutritive  cytoplasm  evolved  to  function  at  a 
distance. 

From  the  elaborate  provision  for  its  protection,  we  mav  infer  that  the 
energy-transforming  function  of  the  brain  has  such  high  selective  value  in 
the  biologic  sense  as  to  confer  a  selective  value  also  on  the  structure  and 
function  of  the  liver  and  of  the  blood;  for  if  the  brain-cells  thus  stri|)ped 
cannot  transform  energy  fast  enough  to  drive  the  muscles  speedily  enough 
to  escape  from  the  enemy,  then  the  liver  and  the  blood  will  perish  as  well  as 
the  brain.  The  more  completely  the  liver  and  the  blood  and  the  lungs  and 
the  kidneys  keep  the  brain-cells  free  from  the  impairing  by-products  of  their 
active  metabolism,  the  cleaner  pair  of  heels  will  the  pursuing  enemy  see. 
It  would  seem  that  if  the  bulk  of  the  brain-cells  were  increased  by  stores  of 
lifeless  food,  their  power  of  attack  and  defence  would  be  diminished. 

The  brain  cannot  work  continuously,  but  a  reversible  process  is  necessary 
at  regular  intervals  to  restore  it.  This  process  in  the  higher  centers  is  called 
sleep.  The  more  intense  the  activation,  the  more  needed  is  sleep.  The 
brain  is  the  only  organ  that  sleeps  conspicuously.  Of  great  significance  is 
the  fact  that  the  entire  man  spends  one-third  of  his  time  waiting  for  the 


RAXSOHOFF  MEMORIAL  VOLUME 


brain   to   restore   itself — to   put   itself   again   in   the   position   of   being  able 
adaptively  to  transform  potential  into  kinetic  energy. 

'l"he  dominating  importance  of  the  brain  is  further  shown  by  the  fact, 
as  Mathews  has  pointed  out.  that  natural  selection  in  the  higher  animals 
has  centered  on  the  brain  and  on  the  brain  alone.  Higher  animals  compete 
through  their  brains.  Hence,  in  the  brain-cells,  we  have  the  highest  devel- 
opment of  a  mechanism  for  transforming  energy,  for  securing  survival 
through  adaptation. 

IS  EXHAUSTIOX  OF  THE  P.RAIX  PRIMARY  OR  SECOXnARV,  OR  BOTH? 

There  is  evidence  that  the  brain  is  both  primarilv  and  secondarily 
involved  in  exhaustion.  Experimental  evidence  of  the  primary  involvement 
of  the  brain  in  the  processes  leading  to  shock  and  exhaustion  is  found  (a)  in 
the  histologic  picture  of  immediate  hyperchromatism  followed  by  progres- 
sive chromatolyses*  ;  (b)  in  immediate  increased  electric  conductivity,  fol- 
lowed by  a  progressive  decrease  below  the  normal*  ;  (c)  in  immediate  alter- 
ation in  the  temperature  of  the  brain  as  evidenced  by  direct  measurements 
with  the  thermocouple.*  Common  experience  demonstrates  that  sudden 
bad  news,  intense  fright,  sudden  severe  pain,  acute  overwhelming  infection, 
cause  an  immediate  loss  of  muscular  and  mental  power.  Further  evidence 
of  the  diminished  power  of  the  brain  to  do  work  in  the  presence  of  an  ade- 
quate blood-pressure  and  respiration  is  seen  during  the  early  stages  of 
physical  exertion,  of  emotion,  of  fever,  of  insomnia,  etc.  Athletes  in  the 
early  stage  of  the  contest  show  no  diminution  of  blood-pressure,  but  they 
do  show  diminished  mental  ])ower. 

In  shock-producing  trauma  of  animals  under  anesthesia,  it  was  usually 
half  an  hour  before  the  blood-pressure  began  to  decline.  What  would  be 
the  physical  power  of  an  animal  thus  traumatized  and  disembowelled  were 
he  allowed  to  recover  from  anesthesia,  even  though  his  blood-pressure  were 
normal?  Captain  Cowell  found  that  the  average  blood-pressure  of  sol- 
diers on  active  trench  duty  were  above  normal,  but  despite  their  high  blood- 
pressure,  these  soldiers  nevertheless  had  to  be  relieved  for  rest  because  of 
their  fatigue. 

In  the  course  of  fevers,  the  blood-pressure  is  usually  higher  than  normal, 
but  the  man  is  prostrated.  In  the  midst  of  acute  grief  or  worry,  the  blood- 
pressure  may  not  be  reduced,  but  the  power  of  the  brain  is  reduced.  A 
rabbit  under  intense  excitation  shows  a  blood-pressure  higher  than  normal, 
but  its  brain-power  is  diminished.  A  brilliant  student,  a  great  military 
strategist,  a  highly  trained  executive  may  suffer  a  breakdown  from  mental 
overwork  and  be  in  a  state  of  brain  exhaustion,  yet  the  blood-pressure  may 
be  normal.  In  the  experimental  laboratory,  in  the  clinic  of  life,  in  the  stress 
of  war,  we  have  reliable  data  from  which  we  conclude  that  the  brain  may 
be  exhausted  primarily  while  the  blood-pressure  may  be  normal,  or  even 


GEORGE  IV.  CRIEE 


higher  than  normal.  The  brain  is  primarily  exhausted  in  insomnia,  in 
which  doubtless  acid  by-products  are  not  produced  faster  than  the  body  is 
able  to  eliminate  them.  The  brain  is  primarily  exhausted  by  anesthetics,  by 
cyanides,  by  acids,  by  lack  of  oxygen,  by  direct  or  reflex  electric  stimulation, 
by  the  excision  of  the  adrenals,  by  the  excision  of  the  liver,  etc.  On  the 
other  hand,  neither  the  brain-cells  nor  any  other  organ,  nor  the  individual 
as  a  whole,  is  immediately  exhausted  by  unlimited  trauma  inflicted  on  areas 
cut  off  from,  connection  witlt  the  brain  by  blocking  the  -nert'c  SH[)ply. 

To  a  less  degree,  but  markedly,  is  exhaustion  from  trauma  or  emotion 
controlled  by  large  doses  of  morphin,  or  by  nitrous  oxid.  Nitrous  oxid 
diminishes  the  oxidation  of  the  brain-cells  and  hence  the  brain  is  less  driven 
by  trauma.  When  exhaustion  or  shock  from  trauma  is  preirentcd  by  block- 
ing the  nerves,  or  when  the  nerves  are  intact,  but  the  brain-cells  are  prevented 
by  nitrous  oxid  from  being  excited  to  action,  not  only  is  the  brain  protected, 
but  the  liver,  the  adrenals,  and  other  organs  are  equally  protected;  the 
blood-pressure  does  not  fall,  and  the  individual  as  a  whole  is  almost  com- 
pletely protected  against  exhaustion.  But  despite  the  fact  that  the  brain 
is  the  primary  factor  in  both  work  and  exhaustion,  the  brain  is  affected  also 
by  many  secondary  causes  of  exhaustion — defective  circulation,  insufficient 
lung  ventilation,  low  blood-pressure,  anemia,  blood  acidosis,  hemorrhage,  lack 
of  oxygen,  disease  of  the  liver,  disease  of  the  adrenals,  etc. 

Apparently  the  more  chemically  receptive  and  reactive  the  tissue,  and 
the  more  highly  it  is  evolved  to  transform  energy,  the  more  readily  is  it 
exhaustible.  Only  cells  have  the  power  of  transforming  energy.  The  cell 
being  the  unit  of  work,  the  cell  equally  is  the  unit  of  exhaustion,  and  the 
brain-cell  is  the  most  readily  exhausted. 

W'e  may  conclude  by  repeating  Sherrington's  statement  that  the  brain 
is  the  master  tissue  of  the  body.  We  have  seen  that  the  brain  is  the  most 
active  energy-transforming  tissue  of  the  body.  We  may  conclude  that 
when  we  speak  of  exhaustion  of  a  man,  we  mean  exhaustion  of  his  brain. 
This  is  the  central  fact. 


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THYROIDECTOMY— A  BRIEF  REXTEW  OF  137  CASES.* 
Joseph  L.  DeCourcv,  M.  D. 

Cincinnati. 

In  October.  1919,  I  published  in  the  American  Journal  of  Surgery  n 
resume  of  fifty-five  cases  of  thyroid  enlargement,  fifty  of  which  were  oper- 
ated upon  under  local  anesthesia  with  but  one  death.  Of  these,  thirty-five 
were  cases  of  well  marked  exophthalmic  goiter.  From  July  1,  1919,  to  July 
1,  1920,  I  have  added  to  this  list  eighty-two  cases  of  thyroid  enlargement, 
with  no  deaths,  making  a  group  of  one  hundred  and  thirty  (130)  operated 
cases  with  but  one  death,  or  a  mortality  in  all  cases  of  less  than  1  per  cent. 
Of  the  last  eighty  cases,  forty-five  were  distinctly  of  the  systemic  or  exoph- 
thalmic type,  while  thirteen  were  toxic  as  regards  metabolic  determination, 
but  were  without  distinct  systemic  sytnptoms.  The  remaining  twenty-two 
were  simple  or  diffuse  parenchymatous  hypertrophies,  or  hypertrophies  of 
the  adenomatous,  colloid  or  fibrous  type. 

Of  the  first  series  of  fifty-five  cases,  five  were  refused  operation  because 
of  their  advancement ;  of  the  second  series  of  eighty-two  cases  only  two  were 
refused  operation  because  of  their  advancement.  One  of  these  receiving  hot 
water  injections  but  left  our  care  before  we  could  determine  any  results ; 
and  the  other  died  after  remaining  in  the  hospital  only  one  week.  In  these 
two  series  arterial  ligation  was  not  resorted  to  in  any  case.  This  greater 
risk  in  the  second  series  being  entirely  due  to  our  greater  confidence  in  the 
use  of  local  anesthesia  in  these  cases.  A  few  inhalations  of  ether  were 
resorted  to  in  only  one  case  during  the  enucleation  of  the  lobes  because  of 
the  panicky  state  of  the  patient.  In  the  remaining  one  hundred  and  twenty- 
nine  (129)  cases  all  were  performed  entirely  under  local  infiltration. 

In  sixty-eight  cases  of  the  second  series,  both  lobes  and  isthmus  were 
removed,  leaving  only  a  small  portion  of  glandular  tissue  at  each  pole.  In 
the  remaining  twelves  cases  the  hypertropheid  portion  alone  was  removed. 

In  the  first  series  of  thirty  exophthalmic  cases  operated  upon,  in  twenty 
I  removed  only  one  lobe.  Five  of  these  cases  returned  for  the  subsequent 
removal  of  the  other  lobe.  I  have  recently  examined  the  fifteen  cases  in 
which  only  one  lobe  was  removed  and  although  they  show  marked  improve- 
ment in  systemic  symptoms,  yet  they  could  not  be  considered  cured.  In 
seven  cases  the  remaining  lobe  has  undergone  compensatory  hypertrophy  and 
the  disfigurement  of  the  neck  therefore  still  remains.  They  have  been  bene- 
fited, however,  to  such  an  extent  that  they  refuse  further  operation. 

Of  the  eighty-three  cases  in  which  both  lobes  and  isthmus  were  removed 
the  improvement  was  immediate  and  permanent.  Approximately  forty-eight 
of  these  cases  have  been  examined  recently  and  although  it  is  only  a  short 
time  since  some  of  them  were  operated  upon,  yet  they  all  may  be  classed 


RANSOHOFF  MEMORIAL  VOLUME 


as  cured,  that  is.  their  heart  action  lias  returned  to  normal  and  increases  only 
slightly  upon  exertion. 

Aside  from  these  series  five  cases  were  treated  indirectly,  that  is.  at- 
tempts were  made  to  eliminate  focal  infections  when  present,  in  order  to 
ascertain  whether  or  not  they  were  the  indirect  causes  of  the  toxic  goiters. 
In  two  of  these  cases  infected  tonsils  were  removed,  in  another  an  infected 
Fallopian  tube  was  removed.  In  the  remaining  two  an  exaggerated  type  of 
chronic  constipation  existed.  One  of  these  cases  was  operated  upon  and  an 
adjustment  of  the  bands  and  membranes  about  the  ileocecal  junction  and  the 
ascending  colon  was  accomplished.  This  patient  also  had  a  retroverted  uterus 
which  was  placed  in  its  proper  position.  The  other  case  was  treated  with 
agar  and  bran  with  occasional  colonic  irrigations. 

These  cases  all  seemed  to  improve  to  some  extent,  but  none  can  be  con- 
sidered cured.  The  goiters  have  not  diminished  perceptibly,  and  the  systemic 
symptoms  still  remain,  so  that  thyroidectomy  will  be  neces.sary. 

After  reviewing  the  foregoing  series  I  have  drawn  the  following  con- 
clusions and  shall  offer  a  few  suggestions  which  I  deem  valuable. 

Reaction  following  various  surgical  methods : 

I  believe  that  in  removing  both  lobes  and  isthmus  at  one  operation  the 
resulting  reaction  is  less  marked  and  therefore  the  post-operative  danger  of 
the  patient  succumbing  to  a  toxemia  caused  by  a  sudden  release  of  the  colloid 
material  is  less  likely,  than  when  only  one  lobe  is  removed,  or  one  thyroid 
artery  tied.  In  other  words,  I  believe  that  the  complete  removal  of  both 
lobes  and  isthmus  at  one  operation  under  local  anesthesia  is  not  more  dan- 
gerous than  the  mere  ligation  of  the  superior  thyroid  artery,  other  condi- 
tions being  equal,  and  I  shall  attempt  to  show  this  with  charts  which  show  the 
pulse  curve.  These  were  chosen  because  of  the  similarity  of  the  cases  as 
regards  blood  pressure,  kidney  function,  heart  dilatation,  etc. 

The  tabulation  following  the  charts  reproduces  the  ])ulse  rate  and  basal 
metabolic  rate  of  the  same  cases. 

I  am  not  placing  the  foregoing  cases  as  a  criterion,  but  I  have  selected 
them  because  of  their  similarity  and  in  order  to  show  the  reactions  follow- 
ing the  various  methods  in  the  same  hands  under  similar  conditions. 

In  other  words,  if  it  can  be  shown  by  sufficient  clinical  data  and  study 
that  the  total  removal  of  the  thyroid  is  just  as  safe  a  procedure  as  the  arte- 
rial ligation,  then  many  months  of  waiting  and  treatment  will  be  saved  the 
individual  patient  and  I  believe  that  harmful  effects  which  continue  to  result 
to  the  other  organs  of  the  body  even  after  two  ligations  will  be  avoided. 

Sand  ford'  has  tabulated  twenty-two  cases  in  which  the  basal  metabolic 
rate  after  two  ligations  has  averaged  plus  39.  This  rate  although  greatly 
reduced  is  undoubtedly  harmful  to  the  human  organs  when  acting  over  a 
period  of  six  to  eight  months,  whereas  with  immediate  bilateral  lobectomy 
the  basal  metabolic  rate  drops  to  between  plus  5  and  plus  16.  which  is 
normal. 


JOSEPH  L.  DcCOURSY 


EFFECTS  OF  FOCAL  IXFECTIOXS  UPON  THYROTOXICOSIS. 
From  the  five  preceding  cases  tabulated  in  which  focal  infections  were 
found  and  eliminated  we  have  come  to  the  conclusion  that  toxic  goiters  in  this 
respect  resemble  tuberculous  glands,  that  is,  although  the  increase  of 
biochemical  jjroducts  may  be  caused  by  bacteria  from  focal  infections,  still 
their  removal  does  not  in  itself  constitute  a  cure,  because  the  thyroid  itself 
during  these  changes  has  become  a  focal  infection,  as  it  were,  secreting  its 
excess  products  which  act  as  a  poison  to  the  body,  just  as  is  the  case  in  tuber- 
culous glands,  and  it  must  be  removed  in  order  to  constitute  a  complete  cure. 

It  has  therefore  been  our  practice  to  remove  focal  infections  where  found 
only  as  a  preliminary  to  the  removal  of  the  thyroid  and  with  no  promise  of 
cure,  just  as  we  sometimes  treat  patients  suffering  with  tuberculous  glands 
of  the  neck  with  tuberculin  preliminary  to  their  removal.  This,  however,  is 
only  our  opinion  based  upon  a  comparatively  few  cases,  and  as  clinical  experi- 
ments dealing  with  focal  infections  progress  and  are  more  accurately  tabu- 
lated a  great  deal  may  be  accomplished  along  this  line  of  endeavor.  The 
failure  to  accomplish  immediate  results  with  the  elimination  of  focal  infec- 
tions up  to  this  time  may  be  the  inability  to  place  one's  finger  upon  the 
ofTending  focus  and  to  be  able  to  say  that  this  and  no  other  is  the  focus  which 
is  accountable.  That  patients  have  been  made  to  undergo  innumerable  oper- 
ations of  a  destructive  nature,  as  the  removal  of  teeth,  appendices,  colon, 
etc.,  without  accomplishing  the  desired  results,  has  long  been  observed. 

Dr.  Frank  Billings-  has  pointed  out  that  it  is  our  duty  to  build  up  the 
resistance  of  our  patients  against  the  organisms  already  in  the  tissues  of  the 
body  even  after  the  true  focus  has  been  removed.  Even  so  I  think  that  some 
improvement  should  be  immediate  after  the  principal  focus  has  been  elim- 
inated, if  it  is  to  be  expected  at  all. 

TESTS  DETERMINING  THYROTOXICOSIS. 
Many  tests  have  been  utilized  and  perfected  in  the  past  few  years,  some 
of  which  promise  to  aid  us  greatly  not  only  in  a  more  correct  diagnosis  of 
each  case,  but  also  in  determining  the  proper  treatment  in  the  various  forms 
of  goiter.  Chief  among  these  is  the  "metabolic  test"  as  made  by  the  Bene- 
dict or  Haldane  apparatus,  McCaskey's  hyperglycemic  test,  etc.  Of  course 
all  of  these  tests,  if  thought  useful,  should  be  used  in  order  to  ascertain  the 
degree  of  toxicity  of  any  given  case,  but  we  should  not  allow  "the  tail  to 
wag  the  dog,"  that  is,  the  surgeon  should  always  refer  to  his  clinical  powers 
of  observation  and  judgment,  and  to  his  operative  experience,  using  every 
useful  laboratory  test  available  to  aid  him  in  his  decision.  The  basal 
metabolic  rate  is  unquestionably  an  improvement  over  the  pulse  rate,  al- 
though its  determinations  in  my  hands  correspond  closely  to  the  pulse  rate. 


KANSOllUin-  MliMORIAL  VOLUME 


Pulse 

P,.  M. 

,  R. 

118 

plus 

74 

EFFKCT  OI' 

KU'.I 

Before 

■  Operation. 

Pulse 

B.  M 

.  R. 

120 

plus 

63 

EFFECT  OF  BILATERAL  THYROIDECTOMY. 

Before  Operation.  About  4  Weeks  After  Operation 

Pulse     P..  Al.  R. 
89  i>lus  20 

OBECTOMY. 

Alu>ut  4  U'eek.^  After  Operation 
Mrss  McDonald:    Pulse     B.  M.  R.  Pulse     W.  M.  R. 

104         ])lus43 

EFFI'TT  OF  LIGATION-  OF  RIGHT  SUPERIOR  TIlYR(-)li:)  ARTI'RY. 

Before  Operation.  About  4  Weeks  After  Operation 

Mrs.  p.:  Pulse     B.  M.  R.  Pulse     P..  M.  R. 

130         plus  76  124         i)1us60 

SI'.I.ECTIC)X  OI"  HEMOSTATS  TO  DETERMIXE  XECESSITV  OF  LIG ATIOX 
IX   THYROIDECTOMY. 

Many  operators  "tie  off"  all  of  their  heiiiostats  while  others  "tie  off"  only 
a  very  few,  "taking  a  chance"  with  must  of  ilieni,  or  even  go  so  far  as  leav- 
ing many  of  them  in  situ."'  By  the  first  method  we  consume  a  great  deal  of 
unnecessary  catgut  into  the  wound,  thereby  inviting  infection  and  causing  a 
greater  reaction  in  the  tissues.  By  the  second  method  we  endanger  the 
patient  with  secondary  hemorrhage  or  hematomata. 

For  the  past  two  years  we  have  been  using  two  different  types  of  hemo- 
stats  in  all  goiter  operations. 

The  types  to  be  used  are  optional  with  the  individual  operator.  We  use 
the  small  Kelly  forceps  and  the  large  Kocher.  \Vhene\er  we  clamp  fascia, 
or  other  structures,  as  muscles,  etc.,  or  small  oozing  points  in  fat,  which 
we  know  will  not  bleed  after  the  clamp  is  removed,  we  use  the  smaller 
forceps;  whenever  we  clamp  an  artery  or  a  large  vein,  or  in  clamping 
through  the  thyroid  gland,  or  in  clamping  any  structure  which  we  know 
will  require  tying  after  the  completion  of  the  operation,  we  use  a  large 
Kocher  forceps. 

It  might  seem  that  this  would  involve  a  great  deal  of  thought  and  loss 
of  time ;  but  we  have  found  that  we  unconsciously  pick  up  the  proper  hemo- 
stat  and,  if  a  nurse  is  passing  instruments,  that  with  only  slight  training 
she  will  hand  the  proper  forceps. 

In  using  this  method  we  ha\e  found  that  we  save  time  in  knowing  which 
hemostat  requires  ligature,  we  prevent  the  possibility  of  secondary  hemor- 
rhage, and  we  also  prevent  the  possibility  of  hemotomata  following  opera- 
tion. Leaving  the  clamps  following  lobe  removal  as  suggested  by  Bartlett' 
becomes  at  once  impractical  because  we  save  an  enormous  amount  of  time 
in  knowing  which  clamps  require  ligature. 


JOSEPH  L.  DcCOURSY 


CONCLUSIONS. 

(1)  Removal  of  both  lobes  and  isthmus  lias  eliminated  in  large  measure 
the  necessity  of  preliminary  ligation. 

(2)  Removal  of  focal  infections  in  itself  is  not  sullicicntly  effective  in 
l)roducing  a  complete  cure  in  thyrotoxicosis. 

(3)  Basal    metabolic    rate   determination   and   other   tests   have    ])ro\en 
themselves  as  definite  aids  to  diagnosis  and  treatment. 

(4)  Greater  risk  can  be  taken  in  operating  under  local  than  with  gen- 
eral narcosis. 


1.  Sandiford,    Hndociinolosy.    \'ol.    IV,   January-March, 

2.  BilHnes,    Discussion    of    Focal    Infections   hy    Fontaii 
June  12,    1920. 

3.  Bartlttt.    ".\n    Kmereoncy    Ti-i  hnic    for    Throideclonv 
July    17,    1920. 


SOURCES  OF  WASSERMAXX  ERROR  AXD  THEIR  CONTROL.* 
By  Albert  Faller.  M.  D. 

Cincinnati. 

That  a  biological  test  be  of  greatest  practical  utility  it  is  necessary  that 
it  be  as  free  from  error  as  possible ;  but  since  all  such  tests  are  more  or  less 
subject  to  error,  it  becomes  essential  that  all  such  possible  sources  be  kiiozvii, 
that  provision  may  be  made  for  their  recognition  and  proper  interpreta- 
tion, and  when  such  errors  are  inherent  and  cannot  be  remedied,  it  becomes 
necessary  to  adopt  a  substitute  test  or  a  modification,  which  is  free  from  such 
error. 

There  is,  perhaps,  no  biological  test  which  has  a  greater  field  of  useful 
application  in  medicine  than  the  W'assermann  complement  fixation  test  for 
syphilis,  which  has  become  almost  indispensable  in  every  field  of  medical 
endeavor.  It  is  to  be  regretted,  however,  that  such  a  test  shduld  at  times 
have  its  usefulness  nullified,  that  it  should  at  times  be  misleading,  that  its 
performance  should  occasionally  lead  us  into  greater  and  more  harmful  error 
than  though  it  had  not  been  performed.  Such,  however,  is  the  status  of  the 
Wassermann  test  as  it  is  commonly  applied  to-day ;  that  these  sources  fif 
error  and  their  control  may  be  sufficiently  accentuated  is  the  apology  for  this 
paper. 

The  causes  of  \\'assermann  error,  inherent  in  the  test  itself,  are: 

1.  Presence  of  but  few  antibodies,  this  resulting  from  (a)  healing  of 
serum;  (b)  effect  of  treatment;  (c)  early  stage  or  .so-called  latency  of 
disease. 

2.  Presence  of  natural  anti-sheep  amboceptor  in  quantities  sufficient  to 
disturb  the  proper  ratio  of  ^^'assermann  factors. 

Noguchi  has  shown  that  during  the  first  five  minutes  of  heating  about  40 
per  cent,  of  antibodies  (reagines)  are  destroyed;  during  the  next  five  min- 
utes 20  per  cent,  disappear,  and  at  the  end  of  inactivation  but  25  per  cent, 
remain.  Thus  the  necessity  for  eonseri'ing  antibodies,  especially  in  inten- 
sively treated  and  in  early  and  latent  cases,  becomes  apparent,  and  as  these 
form  a  great  part  of  the  cases  coming  to  us  for  diagnosis,  it  is  equally  appar- 
ent that  a  large  percentage  of  these  cases  do  not  readily  lend  themselves  to 
the  unmodified  ^\'asse^mann  technique.  These  findings  have  led  the  writer 
to  include  an  active  control  in  every  W'assermann,  and  he  has  refieatedly 
seen  a  barely  perceptible  inhibition  result  in  a  two  plus  positive  reading.  It 
can  readily  been  seen  how  a  negative  report  might  have  been  rendered  in 
these  cases  had  the  straight  W'asserman  technique  alone  been  em])loyed. 

This  is  one  great  group  of  cases  wherein  the  W'asserman  causes  us  to 
give  our  i^atients  tacit  permission  to  de\elop  labe>,  paresis  and  visceral  lues 
in  later  life. 


iber   14,   1914.     Read  before  the  Academy  of  Medicii 


ALBERT  FALLER 


The  second  great  source  of  error  is  the  presence  of  natural  anti-sheep 
amboceptor  in  sufficient  quantity  to  destroy  the  proper  ratio  of  Wassermann 
factors. 

Excess  of  amboceptor  is  disconcerting  only  when  antibodies  are  few. 
It  is  the  writer's  experience  that  blood  containing  enough  natural  anti-sheep 
amboceptor  and  antibodies  to  cause  a  four  plus  reaction,  shows  no  hemo- 
lysis when  considerable  amboceptor  is  added,  but  frequently  does  show  effect 
in  one  plus  cases ;  it  is  loss  of  balance  between  amboceptor  in  excess,  and 
antibodies  deficient  in  amount,  that  causes  negative  reactions  where  posi- 
tives one  should  oljtain  ;  the  smaller  the  amount  of  antibodies  the  more 
probable  that  excess  of  amboceptor  will  destroy  a  delicate  balance ;  where 
antibodies  exist  in  great  number  a  comparatively  rough  approximation  of 
reagent  quantities  may  be  tolerated,  but  in  the  presence  of  small  amounts 
a  most  delicate  manipulation  is  imperative. 

Most  human  blood  contains  enough  anti-sheep  amboceptor  to  hemolyze 
sheep's  corpuscles  in  considerable  quantities.  The  writer  has  frequently 
found  specimens  capable  of  causing  hemolysis  in  proportion  of  one-tenth 
cc.  of  serum  to  1.4  of  sheep's  corpuscles.  Bauer  has  based  his  modification 
upon  the  natural  hemolytic  powers  of  human  serum.  The  complement  of 
human  serum,  while  usually  not  in  great  amount,  is,  nevertheless,  quite  con- 
stantly present,  and  increases  the  effect  of  the  amboceptor.  The  Wasser- 
maiui  technique,  while  demanding  careful  titration  of  amboceptor  added  to 
the  test,  takes  no  cognizance  of  the  amount  of  this  factor  naturally  present 
in  the  serum ;  it  does  not  seem  reasonable  that  a  serum  containing  a  great 
amount  of  amboceptor  should  have  added  to  it  the  same  amount  of  this 
ingredient  demanded  by  a  serum  containing  little  or  none  of  this  body.  It  is 
obvious  that  each  serum  to  be  examined  should  be  titrated  as  carefully  as 
any  other  ingredient  of  the  test ;  each  serum  should  be  individuali::ed;  it 
should  be  carefully  titrated  for  its  amboceptor  and  complement  content ; 
the  presence  of  anti-complementary  substances  should  be  sought  and  a  com- 
parative estimation  of  antibodies  should  be  made. 

To  correct  the  above  errors,  several  modifications  of  the  Wassermann 
test  have  been  proposed ;  all  possess  merit  and  most  possess  as  great  possi- 
bilities for  error  as  does  the  parent  test. 

Bauer,  recognizing  the  fact  that  most  sera  contain  enough  amboceptor 
for  all  hemolytic  purposes,  performs  his  test  exactly  as  does  Wassermann. 
except  that  he  adds  no  amboceptor.  This  would  obviate  one  great  source 
of  error,  but  Bauer,  like  Wassermann,  inactivates,  and,  therefore,  destroys 
reagines,  and  border  line  cases  may  easily  be  overlooked  by  this  method ; 
then,  too,  some  sera  contain  insufficient  amounts  of  amboceptor,  and  in  such 
cases  this  method  would  not  be  applicable. 

Margarita  Stern  ignores  amboceptor  and  utilizes  the  natural  comple- 
ment ;  she  therefore  does  not  inactivate,  thereby  preserving  all  antibodies. 
But  complement  is  the  most  inconstant  and  labile  feature  of  serum  and  it  is 

Pape  HI 


RANSOI/OFI'  MEMORIAL  I'ULUME 


usually  necessary  to  add  complement  from  other  sources ;  then,  too,  there 
is  here  danger  of  excess  of  amboceptor,  as  the  amount  in  the  serum  is  not 
utilized. 

The  writer  considers  the  method  of  Bauer  a  very  useful  modification, 
hut  finds  the  method  of  Stern  of  very  Ihuitcd  utility.  Those  methods  requir- 
ing anti-human  amboceptor  will  not  be  discussed  here,  as  the  writer  has 
had  but  very  limited  experience  with  them. 

Of  all  complement  fi.xation  tests,  the  writer  considers  the  so-called 
Hecht-Weinberg  test  the  most  ti'idely  applicable  and  useful ;  this  method  is 
useful,  not  only  as  a  complement  fixation  test,  but  because  of  the  amount 
of  knowledge  it  yields  concerning  the  pecularities  of  each  serum ;  it  indi- 
cates antibodies;  it  shows  the  presence  of  anti-complementary  substance  and 
the  amount  of  amboceptor  and  complement  present;  armed  with  this  knowl- 
edge, the  serologist  is  in  position  to  properly  interpret  the  significance  of 
the  variutts  tests  and  to  select  the  one  best  suited  to  the  serum  to  be  tested. 

The  Hecht-Weinberg  test  makes  use  of  the  natural  anti-sheep  ambo- 
ceptor and  natural  complement,  and  is  performed  with  nnheatcd  serum;  it 
is  therefore  designed  to  overcome  the  great  sources  of  error  of  the  other 
tests  mentioned;  as  performed  by  the  writer,  it  also  indicates  the  amounts 
of  amboceptor  and  complement  present.  (  Parenthetically,  the  writer  would 
say  he  considers  the  amount  of  natural  amboceptor  of  great  prognostic 
import,  as  he  hopes  to  show  in  a  paper  in  preparation.) 

The  technique,  as  worked  out  by  R.  B.  H.  Gradwohl,  of  St.  Louis,  is  as 
follows:  Fourteen  tubes  are  placed  in  a  rack;  into  each  is  ]:)laced  .1  cc. 
of  serum  to  be  examined ;  then  into  the  first  ten  tubes  is  i)laced  descending 
amounts  of  salt  solution,  in  the  first  tube  .9  cc.  descendinij  to  .1  cc.  Then 
in  these  ten  tubes  is  jilaced  ascending  amount  of  shee])'s  corpuscles,  begin- 
ning with  .1  cc,  and  ending  with  .1  cc.  This  gives  each  of  the  first  ten  tubes 
equal  volume ;  these  ten  tubes  are  for  the  purpose  of  obtaining  the  hemolytic 
index — the  hemolizing  power  of  the  serum.  In  the  next  three  tubes  is  placed 
graded  amounts  of  antigen,  .2  cc,  .15  cc.  and  .1  cc.  The  last  tube  contains 
only  serum  and  is  the  control  tube;  these  four  are  then  brought  to  equal 
volume  with  salt  solution. 

The  rack  is  then  placed  in  the  water  bath  for  one-half  hour  and  shaken 
frequently.  That  tube  which  shows  complete  hemolysis  of  the  greatest 
amount  of  sheep's  corpuscles  is  then  noted,  and  gives  the  hemolytic  index. 
Blood  corpuscles  are  then  added  to  the  last  four  tubes  according  to  this 
index:  if  this  is  from  one  to  four,  we  add  .1  cc.  of  corpuscles;  if  from  five 
to  seven,  .15  cc,  and  if  eight  or  more  we  add  .2  cc.  The  rack  is  again 
placed  in  the  water  bath  and  results  read  as  in  the  \\'assermann,  when  the 
control  tube  shows  complete  hemolysis. 

It  is  the  universal  ex])erience  that  a  once  negative  W  assermann  may 
frcqiieiilly  bccduic  pusiiivc;  a  proof  that  infection,  howcxi-r  sm;ill  in  amount, 
slill  existed;  il  is  the  writer's  experience  (and  that  of  1\.  B.  II.  (iradwohl. 


ALBilRT  PALLIIR 

who  has  had  an  enormous  experience  with  this  test)  that  when  the  blood 
becomes  negative  to  the  Heclit-Weinberg.  it  usually  remains  so.  This,  in 
connection  with  the  fact  that  the  Hecht-Weinberg  is  positive  in  the  early 
primary  stages  of  lues  and  in  well  treated  and  latent  cases,  indicates  that  the 
smallest  amount  of  systemic  infectioti  causes  reaction  to  this  test. 

To  illustrate  the  absolute  necessity  for  Wassermann  modification  and  for 
obtaining  the  hemolytic  index,  the  following  cases  may  be  cited: 

Case  of  S.  L.  Hemolytic  index  10,  amboceptor  content  14,  Wassermann 
tests  with  heated  and  unheated  serum  are  negative ;  the  Bauer  and  liecht- 
Weinberg  tests  are  two  i)lus  positive.  This  is  no  doubt  a  negative  W'asser- 
mann  in  a  positive  case  of  lues  due  to  excess  of  amboceptor.  This  case  one 
month  ago,  with  an  index  of  6  gave  a  slightly  positive  Wassermann.  Infec- 
tion in  this  case  occurred  twenty  years  ago. 

Case  of  R.  L. :  Has  a  chancre  of  se\-en  days'  duratiun  ;  no  other  lesion 
apparent:  hemolytic  index  is  10,  amljoceptor  content  is  14;  Wassermann, 
heated  and  unheated,  as  well  as  the  ]5auer  test,  are  negative;  the  Hecht- 
Weinberg  is  one  plus  ]K>sitivc.  Here  the  straight  Wassermann  is  negative 
because  of  the  destruction  of  the  few  anti-bodies  i^resent  and  also  because 
of  the  large  amboceptor  content ;  this  content  also  interferes  with  the  active 
Wassermann ;  the  leaner  test  is  negative  because  of  inactivation ;  the  Hecht- 
Weinberg,  utilizing  a  natural  amljoceptor,  and  preserx'ing  all  antibodies,  is 
slightly  positive. 

Case  of  J.  C,  a  hospital  case,  was  admitted  because  of  suspected  diph- 
theria; has  a  necrotic  tonsil;  hemolytic  index  is  10;  amboceptor  content  is 
15;  all  tests  are  four  plus  positive,  excess  of  amboceptor  and  heating  of 
serum  not  influencing  results  in  the  presence  of  excessive  amounts  of  anti- 
bodies. 

Case  of  W.  T. :  Has  no  index,  both  amboceptor  and  complement  being 
entirely  absent ;  gives  a  slightly  positive  reaction  with  the  unheated  \\  asser- 
mann ;  negative  to  the  regular  ^^'assermann.  Having  no  amboceptor  or  com- 
jilement,  this  serum  was  not  suited  to  the  Hecht-Weinberg  test ;  having  no 
amboceptor  and  but  few  antibodies,  it  was  not  suited  to  the  Bauer  test :  hav- 
ing no  complement,  it  was  not  suited  to  the  Stern  test,  and  having  but  few 
antibodies,  it  could  not  be  heated  for  the  regular  Wassermann.  Any  test, 
other  than  the  unheated  Wassermann,  would  have  resulted  in  error.  This  is 
a  well  treated  case  of  paresis,  where  the  original  Wassermann  gave  a  four 
plus  positive  reading.    This  case  is  now  negative  to  unheated  Wassermann. 

Such  cases  as  these  indicate  that  there  is  no  one  best  method  of  testing 
all  specimens  of  serum,  and  the  writer  wishes  to  especially  emphasize  this 
fact.  If  amboceptor  is  present  in  great  amount,  with  enough  antibodies  to 
tolerate  in  activation,  the  Bauer  test  is  acceptalile;  if  amboceptor  and  com- 
plement are  present  in  sufficient  (|uanlity,  and  no  anti-comi)lementary  sub- 
stances arc  ])resent,  then  the  Hecht-Weinberg,  be  the  antibodies  many  or 
few:  with  low  amboceptor  and  low  complement  content  and  few  antibodies 


RANSOHOFF  MEMORIAL  VOLUME 


assumed,  and  no  anti-complementary  substances,  the  unlieated  Wassermann ; 
in  all  cases  of  anti-complementary  substances,  the  regular  Wassermann  must 
be  relied  upon. 

In  conclusion,  the  writer  would  say  that,  in  trying  to  simplify  Wasser- 
mann and  allied  reactions,  one  is  led  far  afield  into  the  domain  of  ferment 
possibilities,  and  if  we  would  make  this  field  free  from  error,  we  must 
increase,  rather  than  decrease,  its  complexities.  The  ideal  condition  for 
complement  fixation  work  is  first  to  become  thoroughly  familiar  with  the 
serum  to  be  tested ;  titrate  it  as  thoroughly  as  any  other  integer  of  the  test ; 
see  where  its  error  would  most  likely  occur;  and  assign  the  chief  signifi- 
cance to  that  test  which  you  consider  the  ideal  one  for  that  serum. 


PRIMITIVE  SURGERY  OF  THE  WESTERN  HEMISPHERE.* 
Leonard  Freeman.  M.  D. 
Denver. 

I  have  selected  this  subject  for  my  address,  because  it  seems  peculiarly 
appropriate  to  bring  before  the  Western  Surgical  Association  something 
about  the  prehistoric  surgery  of  the  West,  which,  as  far  as  I  am  aware,  has 
not  been  done  before. 

Two  causes  of  surgical  and  medical  ailments  were  universally  recognized 
among  the  early  inhabitants  of  the  Americas,  one  natural  and  the  other  super- 
natural. If  the  cause  was  not  easily  perceived,  as  was  often  the  case,  it  was 
regarded  as  supernatural.  The  supernatural  diseases  were  supposed  to  orig- 
inate in  various  ways:  by  the  casting  of  spells,  by  contact  with  some  objec- 
tionable person  or  thing,  or  by  the  presence  of  something  in  the  system,  such 
as  an  evil  spirit,  a  stone,  a  piece  of  wood,  a  worm  or  an  insect.  Manifestly, 
they  came  just  as  near  to  the  recognition  of  bacteria  as  they  could  without 
knowing  anything  about  them. 

It  must  not  be  thought,  however,  that  real  causes  were  not  given  their 
due  significance,  if  they  made  themselves  sufficiently  apparent,  as  often  hap- 
pened in  surgical  lesions  at  least.  The  ancient  members  of  our  profession 
were  by  no  means  always  as  childish  as  they  are  sometimes  represented  to  be. 
It  goes  without  saying  that  supernatural  ailments  can  be  treated  by  super- 
natural means  only,  which  accounts  for  the  existence  of  the  so-called  medi- 
cine-man, with  his  impressive  fetishes,  antics  and  incantations.  In  this  con- 
nection it  should  be  understood  that  the  word  "medicine"  was  not  confined 
originally  to  material  remedies,  but  had  in  addition  a  magical  and  super- 
natural significance.  Hence  a  "medicine-man"  was  not  only  a  physician  in 
our  sense  of  the  word,  but  was  also  a  sort  of  priest,  prophet,  magician  and 
all-around  dealer  in  the  mysterious. 

THE  MEDICINE-MAN. 
The  medicine-man^  was  usually  a  person  of  more  than  ordinary  tact, 
knowledge  and  intellect.  In  addition  to  being  a  surgical  and  medical  author- 
itv,  he  also  was  consulted  on  many  things  concerning  the  spiritual  and  tem- 
poral welfare  of  his  people.  Although  dealing  extensively  in  the  occult,  he 
had  a  dignified  and  firm  belief  in  himself  and  his  methods,  and  was  much  in 


•Presidential  addr 

ess  deliv. 

:red  before  the  Western  Surgical  Association,  Omaha,   Dec.   14,    1917. 

From  The  Jou 

rnal  of  the  Amer 

ican  Medical  Associa 

ition,  Feb. 

16,   1918. 

1.     Althoi 

..gh    the 

title   is   I 

nasculine,   it   is   inte 

resting   to 

note   that 

there   were 

also   "medicine- 

women,"  who  held  high  places  i, 

n  the  profession  and 

no  doubt  deserved  the  confidenc 

re  placed  in  them 

by    their    clien 

tele.      The    costu 

me    and    make-up    of 

;    a    typical 

medicine 

■man    is    well    described    by 

M'Clcnachan: 

"The   face  is  painted,  usuall'y  red,  « 

ath  yellow 

trimmings 

i  about  the 

eyes  and  mouth. 

The  hair,  alwa 

long,   h. 

IS  a  tuft  of  feathers 

braided  in 

at  the  crown;   and 

to  braids  of  hair 

hanging   about 

the   shoulders   ar 

e   attached   horsehaii 

-5,    snake   r 

attles,   she 

lis,   etc.;    o' 

vfer  all    is    dusted 

red   and  yellov 

1   paint. 

The   ea 

rs   are   pierced   by   n 

ngs,    and 

suspended 

from   them   hang 

shells,    reaching  tn   the 

shouldei 

-s.    .Uout    the    neck 

are   strings 

of   brighl 

:    colored    b< 

eads,    with    bird's 

claws,  pebbles, 

buffalo 

teeth,  etc 

:.     The  wearing  apparel  consist! 

i  of  a  shii 

■t  made  of 

rawhide,   leggins. 

breech  clout,  moccasins 

..  and  ovs 

■r  all  a  blanket  or  buffalo  robe. 

The  shir 

t  is  daubed 

with  paint,  with 

some  hideous  i 

1  the  bre: 

.St.     The  leggins  are 

made  to  fit  closely. 

but  with  a 

wide  strip  along 

the  outside,  to 

which  i! 

;  attached  beads,  bones,  etc.     ' 

The  blanket 

;  or  robe. 

in  either  ca 

se  gaily  adorned. 

is  loosely   thro 

wn  over 

the  shou 

ilders."      Of  the  mcc 

licine-man's 

methods 

nt.   Hrdlicka  sue- 

RAXSOUOFF  MFM0RL4L  J -GLUME 


earnest  in  spite  of  the  legerdemain  and  grotesque  dress  and  actions  that  he 
employed  to  emphasize  his  doings  and  impress  their  importance  on  the 
observer.  There  is  even  reason  to  believe  that  his  fantastic  dances  and  ges- 
tures, facial  contortions  and  weird  chantings  exercised  a  hypnotic  influence 
on  his  patients,  leading  to  relaxation  and  sleep,  which  may  have  facilitated 
the  recovery  of  some  who  would  have  been  given  up  to  die  by  more  civilized 
practitioners.  In  fact,  w^hen  one  comes  to  think  of  it,  such  things  are  merelv 
an  exaggeration  of  that  "personal  influence"  which  every  physician  is  sup- 
posed to  exercise  in  greater  or  less  amount. 

To  a  certain  extent,  the  medicine-man  was  the  ])rotector  of  the  perse- 


Fig.  1.     Head  of  Peruvian  mummy,  showmg  trephine  opening  in  left  temporal  region, 
and  an  apparent  right   facial  paralysis   (  U.  S.   Ethnological  Reports). 

cuted.  and  the  refuge  of  the  fugitive.  Even  an  enemy  could  find  sanctuary 
in  a  medicine-lodge,  where  his  wounds  were  dressed  and  his  other  needs 
attended  to.  We  should  indeed  be  proud  that  this  same  spirit  has  always 
characterized  the  medical  profession  at  all  times,  and  that  it  still  exists 
among  us.  Looked  at  from  this  point  of  view,  the  Red  Cross  is  a  great 
medicine-lodge. 

It  was  not  much  easier  to  become  a  "nu-dicinc-man"  in  those  (lavs  than 


allv  ct;.  '  !  11'?  or  kneariinp   ( s-ii.- i  u  .  -    j.n.    \  i.        i,   i  .>,il:Ii  employed  more  commonly 

,r  siipl"  '    '    "—'■'"''•■  1'.,,,^,!  ini.li^uu    iia>.  U.l  ,-kii..  ^ /.'.i  .lUion  of  the  objective  cause  of 

e  di-.  .  ;      !      .  nlo  the  patient,  passes  wiili  tiiicers  moistened  with  saliva, 

remnii  ^    l  lintinR  of  the  body  of  the  patient  as  well   as  that  of  the 

ediciiK  iiMises    (made   with  voice,   rattle  or  drum),  commands  and 

ihort.di    '      t  i  :     t-,    i-Miiances  given  the  patient,  various  symbolic  representatives, 

irification  nl  llie  tjiulv  liv  swt-rit  t>atlis.  purging  and  emesis,  strong  sucking,  cauterizing,  sacrifying, 
ceding,  e-xternal  applications,  the  administration,  externally  or  internally,  of  secret  magic  or  other 
edicine,  and  various  regulations  of  the  behavior  of  the  patient.  In  the  larger  curat" 
veral    medicinemen    acted    conjointly,    or,    if   but   one    present,    he   may    have   from 


LEONARD  FREEMAN 


it  is  now.  The  usual  method  was  to  spend  at  least  a  year  with  a  preceptor, 
paying  him  well  for  his  instruction.  There  was  much  to  be  learned  and 
remembered,  for  these  preceptors  all  varied  in  their  bewildering  practices, 
and  it  was  customary  to  study  under  more  than  one.  As  with  the  modern 
doctor,  even  after  graduation  the  life  of  the  medicine-man  was  not  one  of 
pampered  ease.  He  was  compelled  to  resjjond  to  every  call,  night  or  day: 
although  the  Pueblos  permitted  an  exception  to  the  rule,  if  the  unwilling 
physician  could  catch  the  messenger  within  a  given  distance  and  kick  him. 
How  many  of  us  wish  we  had  the  same  privilege. 

\l  the  patient  died,  the  doctor  also  ran  the  risk  of  death,  at  the  hands  of 
the  relatives ;  and,  at  the  very  least,  a  number  of  failures  to  cure  led  to  a 
loss  of  reputation  and  final  dismissal  from  the  profession.  There  was,  how- 
ever, a  saving  clause,  at  least  among  the  Pueblos,  for  when  the  medicine- 
man's power  began   to   wane  he   could   rejuvenate   it  by   rubbing  his   b;ick 


Fig.  2.     Scjuare  trepliinc  opening   ( U.  .'^.  Etlinolngical  Reports 


against  a  certain  sacred  stone.  The  location  of  one  of  these  stones  is  still 
known.  The  fees  were  of  good  size  and  paid  promptly,  often  in  advance. 
They  consisted,  not  luilike  those  of  a  country  doctor,  of  such  things  as 
blankets,  horses,  skins,  weapons  and  various  other  personal  effects.  It 
should  be  emphasized,  however,  that  to  the  credit  of  the  profession  much 
charity  work  was  done  then,  just  as  it  is  now. 

Curiously  enough,  there  exists  throughout  the  world  a  marked  similaritv 
in  prnnitive  medicine  which  suggests,  perhaps,  a  common  origin  of  the  vari- 
ous races.  In  accordance  with  this,  the  metliods  of  treatment  were  often 
identical  among  the  prehistoric  peoples  of  North,  South,  and  Central  Amer- 
ica, including  the  Indians,  the  Pueblos,  the  Aztecs  and  the  Incas.  The  old 
Spaniards  were  in  a  position  to  observe  these  things  and  should  have  been 
able  to  tell  us  much  about  them;  but  unfortunately  those  aggressive  pioneers 
were  more  interested  in  killing  than  in  curing,  so  that  their  descriptions  ^re 


RANSOHOFF  MEMORIAL  VOLUME 


unsatisfactory  and  meager.  Enough  has  been  handed  down,  however,  to 
make  it  clear  that  considerable  crude  but  efficient  surgery  was  practiced,  some 
of  it  being  done  in  hospitals,  at  least  in  Mexico. 

PRIMITIVE  AMERICAN   SURGERY. 
Let  us  consider  this  primitive  American  surgery  more  in  detail : 


Fig.  3.     Large  antemortem  trephine  opening   ( U.   S.   Ethnological   Reports). 

Trephining.- — As  is  well  known,  this  is  one  of  the  very  oldest  surgical 
operations,  and  was  extensively  practiced  by  prehistoric  peoples  everywhere. 
It  is  probable  that  it  was  done  not  only  for  therapeutic  purposes,  but  for 
other  reasons  as  well ;  for  instance,  to  let  out  evil  spirits,  to  obtain  amulets 
for  decorative  and  other  uses,  or  merely  as  a  religious  rite.  The  wearing  of 
amulets  made  from  sections  of  skulls  was  a  common  custom  among  the 
earlier  inhabitants  of  the  world.  They  were  mostly  obtained  postmortem, 
but  some  were  evidently  removed  froin  living  captives,  possibly  with  the 
idea  that  they  were  more  potent  as  talismans  against  disease,  or  that  they 
conferred  on  the  wearer  the  physical  or  mental  powers  of  the  original  owner.' 
But  there  can  be  no  question  that  much  trephining  was  also  done  for  thera- 
peutic purposes — for  fracture,  epilepsy,  insanity,  convulsions,  headaches, 
etc.— as  it  is  among  various  primitive  races  to-day. 

According  to  archeologists,  trephining  was  done  far  more  frequently  in 
Peru  and  Bolivia  than  in  any  other  parts  of  the  Western  Hemisphere. 
Among  12,000  skulls  from  Bolivia,  for  example,  5  per  cent,  had  undergone 
this  operation,  and  in  Peru  the  percentage  was  not  much  less,  showing  that 
the  procedure  was  much  more  common  then  than  now.  Less  is  known  about 
trephining  in  the  United  States,  although  occasional  skulls  with  the  charac- 


LEONARD  FREEMAN 


teristic  openings  have  been  found  in  the  tumuli  of  the  mound  builders.     It 
was  more  frequent,  however,  in  Mexico  and  Central  America. 

Although  many  of  the  operations  were  done  postmortem,  others  were 
antemortem,  as  is  shown  by  the  growth  of  bone  around  the  edges  of  the 
openings.  It  may  be  inferred  that  some  of  the  patients  died  during  the 
operation,  the  button  having  been  outlined  but  not  removed.  We  can  well 
imagine  that  a  "death  on  the  table"  must  have  been  accompanied  with  the 
.same  bitter  regret  and  disappointment  as  it  is  now. 


Fig.  4.     Ahiltiple  antemortem  trephine  openinf;s  (U.  S.  Ethnological  Reports) 


We  are  justified  in  believing  that  these  surgical  interventions  were  fre- 
quently for  therapeutic  purposes,  because  fractures  are  often  found  in  con- 
nection with  them ;  and  even  when  no  fracture  can  be  seen,  it  is  not  unrea- 
sonable to  suppose  that  a  puncture  of  the  skull,  such  as  must  have  been 
frequent  from  the  spiked  war  clubs  then  in  use,  may  have  existed  and  been 
removed  by  the  operation.  And,  in  addition,  the  fact  that  the  openings  were 
sometimes  at  a  distance  from  the  break  in  the  bone  might  well  mean  that  the 
principle  of  decompression  was  recognized-^perhaps  learned  from  experi- 
ence in  trephining  for  headaches,  epilepsy,  insanity,  etc.  In  fact,  if  we  do 
not  regard  these  operations  as  deliberate  decompressions,  they  would  seem 
to  be  purposeless. 

In  the  Smithsonian  collection  is  the  skull  of  a  Peruvian  muiumy  on 
which  the  dried  soft  parts  are  still  in  place.  A  trephining  has  been  done  at 
the  seat  of  a  fracture  in  the  left  temporal  region,  the  interesting  point  being 
that  the  face  is  strongly  drawn  to  one  side,  apparently  the  result  of  paral- 
ysis— a  most  uncanny  phenomenon,  to  say  the  least  (Fig.  1). 

Most  of  the  trephining  operations  in  America  do  not  seem  to  have  been 
done  very  skilfully.  They  were  crude  jobs  with  crude  tools  that  often 
slipped  during  the  laborious  process,  as  shown  by  scratches  on  the  adjacent 
parts  of  the  skull. 

The  shape  of  the  opening  was  usually  square  or  oblong,  although  some- 
times round  or  oval.    The  square  opening  (Fig.  2)  was  peculiar  to  South 


RANSOIIOFf  MEMORIAL  J-QLl'MF. 


America.  It  was  made  by  cutting  four  rectangular  intersecting  grooves, 
almost  but  not  quite  through  the  bone,  and  then  prying  out  the  loosened  piece 
of  skull.  The  round  openings  (Figs.  3  and  4)  were  produced  by  gradual 
scraping,  as  shown  by  the  characteristic  of  uncompleted  operations. 

From  the  nature  of  the  grooves  and  the  lines  on  their  sides,  it  is  jDrob- 
able  that  they  were  cut  with  a  stone  instrument,  like  a  spear  head,  set  in  a 
handle  and  possessing  a  rough  and  rather  blunt  point — a  kind  of  single- 
toothed,  stone  saw,  as  it  were,  by  means  of  which  the  bone  was  slowly  worn 
away  by  a  to-and-fro  motion  aided  by  strong  pressure.  It  is  likely  that  the 
round  holes  were  scraped  out  with  sharp  flakes  of  flint  or  obsidian,  as  is 
still  done  by  certain  more  or  less  uncivilized  tribes  in  various  countries. 

For  a  number  of  reasons,  it  is  supposed  that  the  patient's  head  was  held 
between  the  knees  of  the  operator,  who  laid  open  the  scalp  with  a  crucial 
incision  and  then  sawed,  scraped  and  pried  away  at  the  unfortunate  vie- 


/ 

: 

1 

m 

J     ■ 

Fig. 


Splint  made  of  sticks  held  together  by  strips  of  rawhide 
(Medical    and    Snrgical   Reporter.   1879,   2). 


tim's  calvarium.  with  many  slips  of  his  crude  instrument,  until  an  opening 
was  made.  The  time  required,  as  established  by  experiment,  must  have  been 
at  least  an  hour  and  often  much  longer. 

It  may  have  been  that  some  sort  of  anesthetic  was  employed,  such  as 
was  used  by  the  Pueblo  Indians ;  but  if  not.  what  a  nightmare  of  an  experi- 
ence it  must  have  been  for  the  patient,  to  say  nothing  of  the  nervous  strain 
on  the  surgeon ;  although,  when  one  considers  the  matter  calmly,  it  could 
not  have  been  much  worse  than  the  torture  occasionally  inflicted  on  us  by 
our  dentists.    After  all,  much  depends  on  the  point  of  view. 

It  should  be  mentioned  that  trephining  is  still  practiced  in  the  same  primi- 
tive manner  by  native  medicine-men  in  the  mountains  of  Peru,  although  they 
now  employ  pocket  knives,  chisels,  etc.,  instead  of  instruments  of  stone.    The 


LFAINARD  FREEMAN 


operation  is  generally  done  for  fracture,  and  is  surrounded  by  great  secrecy 
and  certain  mystic  rites.     It  is  said  to  be  quite  successful. 

Fractures. — In  the  treatment  of  broken  bones,  the  results  were  often 
surprisingly  good.  It  was  cuslomary  to  set  them,  more  or  less  skilfully,  by 
pulling  and  manipulation  ;  bul  permanent  extension  was  not  often,  if  ever, 
employed.  Splints  of  \ariims  kinds  were  in  universal  use.  They  frequently 
were  made  of  bark,  tin-  natural  curves  of  which  facilitated  adjustment  to 
the  limb,  especially  after  soaking  in  hot  water  and  cutting  away  portions  to 
accommodate  bony  prominences  about  the  joints,  (irass,  scrapings  from 
tanned  hides,  and  other  soft  substances  were  used  for  padding.  ( )cca>ion- 
ally  the  splint  was  filled  with  moist  clay,  which  enclosed  the  limb  somewhat 


splints  found  in  anc 
the  Stale  Histc 


n  clift  dwellings  of  southwestern  Coloi 
cal  and  Natural   Histor\    Society,  Denv 


like  a  plaster  cast,  and  must  have  been  both  comfortable  and  effective.  A 
window  was  aKvays  left  o\er  the  site  of  a  compound  fracture  to  permit  of 
attention  to  the  wound. 

Other  sorts  of  splints  were  made  from  sticks  or  ])liablc  branches,  such  as 
green  willows,  held  together  by  strips  of  bark  or  leather  (Fig.  5).  The  Cliff 
Dwellers  of  the  Southwest,  who  from  their  mode  of  life  must  have  broken 
their  bones  often,  knew  how  to  manufacture  splints  that  scarcely  could  be 
improved  on.  Specimens  exhibited  in  the  Museum  of  the  State  Historical 
and  Natural  History  Society,  Denver,  are  beautifully  made  from  polished 
wood  and  correctly  curved  to  fit  the  limbs  for  which  they  were  intended,  the 
edges  being  nicely  rounded  to  prevent  injury  to  the  skin  (Fig.  6).  Similar 
splints  were  employed  by  the  Aztecs. 

Often  the  splints  were  removed  and  the  limb  massaged,  a  practice  that 
gives  good  results  and  deserves  more  attention  than  is  given  to  it  by  modern 
surgeons. 

In  the  treatiuent  of  fractures,  the  Hopi  Indians  employ  s])linters  of  trees 
which  have  been  struck  by  lightning ;  not,  however,  as  splints,  but  merely  as 
fetishes.  For  some  reason  or  other,  they  believe  that  those  who  have  them- 
selves received  a  lightning  stroke  are  possessed  of  special  skill  in  the  care 
of  broken  bones — rather  a  severe  requirement  for  a  sjiecialist  in  fractures, 
one  would  think. 


RANSOM  OFF  MEMORIAL  VOLUME 


In  the  Field  Museum,  Chicago,  is  exhibited  an  excellent  pair  of  well 
crutches  from  the  clifif  dwellings  of  southern  Utah  (Fig.  7). 

Dislocation. — The  reduction  of  many  of  the  simpler  forms  of  dislocation 
was  quite  generally  practiced,  both  by  extension  and  by  manipulation,  al- 
though the  methods  were  of  course  empiric  and  without  scientific  foundation. 

Treatment  of  JVounds. — The  suturing  of  incised  wounds  was  a  common 
procedure ;  but  it  was  considered  so  necessary  that  free  suppuration  should 
occur  that  thin  pieces  of  bark  were  sometimes  placed  between  the  edges  in 
order  to  check  primary  union.  The  sutures  were  obtained  from  animal 
tendons,  human  hair  or  plant  fibers.  The  tendons  were  smoked  hard  and 
dry  and  were  not  absorbed,  but  were  removed  in  about  a  week.    It  was  cus- 


Fig,  7.     Crutches  found  in  cliff  dwelling  of  .southern  Utah   (Field   Museum,  Chicago). 

tomary  to  provide  for  ample  drainage,  which  was  often   facilitated  by  the 
insertion  of  strips  of  bark  or  other  material. 

The  frequent  washing  of  all  sorts  of  wounds,  perhaps  several  times 
daily,  was  universally  practiced,  and  may  have  had  much  to  do  with  the 
rapid,  not  to  say  astounding,  recoveries  that  are  said  frequently  to  have 
occurred.  The  irrigations  were  made  with  simple  cold  water  or 
with  decoctions  of  certain  things,  such  as  basswood,  willow,  slippery  elm, 
lichens  and  various  herbs.  In  addition,  the  wounds  were  often  packed  with 
charcoal,  ashes,  piiion  gum  and  other  balsams,  or  sprinkled  with  these  sub- 
stances in  the  form  of  powder.  Most  of  the  balsams  and  decoctions  prob- 
ably had  more  or  less  of  an  antiseptic  action,  but  it  is  questionable  if  this 
was  sufficient  to  be  of  much  value. 

Page  JUS 


LEONARD  FREEMAN 


Saliva,  both  pure  and  mixed  witli  other  things,  was  very  generally  used ; 
in  fact,  it  was  quite  the  proper  thing  for  a  physician  to  spit  on  a  wound  or 
into  the  materials  used  in  its  treatment.  What  consternation  such  a  pro- 
ceeding would  produce  in  the  operating  room  of  a  modern  hospital !  Never- 
theless, we  should  not  forget  that  animals  always  lick  their  injuries,  and  that 
lesions  about  the  mouth  heal  even  more  readily  than  elsewhere.  Another 
revolting  custom,  according  to  our  point  of  view,  was  the  sucking  of  pus  out 
of  wounds — a  much  valued  method  of  treatment. 

In  Brazil,  large  open  wounds  of  the  extremities  were  sometiines  handled 
in  an  extremely  interesting  manner.  The  part  was  wrapped  in  the  inner 
bark  of  a  tree,  and  suspended  on  a  frame  over  a  bed  of  glowing  coals  until 
nearly  roasted.  This  method  was  painful,  but  is  said  to  have  been  effective, 
primary  union  often  resulting  within  a  few  days  under  the  most  unpromis- 
ing circumstances.^ 

Although  there  is  little  evidence  that  actual  laparotomies  were  ever  per- 
formed, we  at  least  know,  from  a  description  of  an  operation  witnessed  early 
in  the  seventeenth  century  by  Bernabe  Cobo,  that  they  were  sometimes 
"faked"  for  psychologic  purposes.  He  says:  "The  sorcerers  (medicine- 
men) did  as  if  they  would  open  him  by  the  middle  of  the  body  with  knives 
.of  crystalline  stone,  and  they  took  out  of  his  abdomen  snakes,  toads  and 
other  repulsive  objects."  However,  when  we  remember  with  what  dexterity 
the  human  body  was  opened  for  sacrificial  purposes  by  the  Aztecs,  it  should 
not  be  surprising  if  they  sometimes  performed  operations  on  the  internal 
organs 

Punctured  IVoiinds. — Among  the  Pueblos,  especially,  no  attempt  was 
made  primarily  to  remove  foreign  bodies,  such  as  arrow  heads ;  but  they 
were  gradually  forced  out  by  firm  kneeding  and  pressure  applied  to  the  sur- 
rounding parts.  It  was  sometimes  necessary  to  continue  this  painful  pro- 
cedure for  several  days,  although  in  the  end  it  was  generally  successful ; 
but  if  it  failed,  an  operation  was  done,  through  a  crucial  incision.  Irriga- 
tions with  various  decoctions  were  frequently  practiced.  These  were  some- 
times squirted  deep  into  the  openings  through  a  quill  or  a  hollow  bone  by 
means  of  the  mouth  or  a  syringe  made  from  a  bladder.  Some  of  these 
primitive  surgeons  used  sticks  wrapped  with  cotton  to  swab  out  punctured 
wounds,  as  part  of  the  general  program  of  cleanliness,  which,  although  they 
lacked  the  Dakin's  solution,  nevertheless  reminds  one  of  the  methods  of 
Carrel.  The  cleaning  of  punctured  wounds  by  sucking  out  the  pus  with  the 
mouth  was  an  ordinary  and  widely  spread  custom,  which  undoubtedly  pos- 
sessed merit  in  spite  of  its  objectionable  features. 

Treatment  by  Suction. — This  was  done  with  the  mouth,  either  directly 
or  through  a  tube  of  stone,  wood  or  bone  (Fig.  8).     In  this  way  pus  was 

liiins  ntc;isi<.iii;illy   did   quite  good  surgery   is  evidenced  by  an 
iiifl-itiM  .1   :m.l  i'.iiiprenous  foot.     The  trouble  was  supposed  to 

.n Tied  out  for  the  purpose  of  dislodging  it. 

!       ncl   the  bone  scraped.     The   wound  was  then 
1,1  ind  bandaged.     The  final    results   was  satis- 


3. 

That 

the 

North   Amc. 

operatio 

nessed  by  Cushin 

h\  due 

■rious  magK"! 

A  cruci 

al  inci 

was  made,   l 

repeatedly   irr 

icate 

■d,  packed  ^^ 

factory. 

Could  a 

RANSOHOFF  MEMORIAL  VOLUME 


removed  from  wounds,  ulcere  and  abscesses,  and  tlie  vascular  circulation 
])romoted,  thus  calling  to  mind  the  modern  suction  treatment  advocated  by 
Bier.  Even  the  thought  of  using  the  mouth  directly  for  such  purposes  is 
repulsive,  but  the  danger  to  the  physician  was  slight  and  the  method  was 
undoubtedly  efifective.  After  all,  was  it  much  worse  than  the  many  grue- 
some things  done  by  medical  students  in  the  dissecting  room?  In  Bolivia, 
at  the  present  time,  medicine-men  have  been  seen  to  suck  sujipurating 
wounds  and  even  syphilitic  ulcers.  Men  who  were  thus  willing  to  sacrifice 
themselves  for  the  welfare  of  their  patients  should  be  respected  and  not 
ridiculed,  just  as  we  honor  the  young  physician  who  heroically  applies  his 
mouth  to  a  tracheotomy  wound  in  a  case  of  diphtheria. 

The  imaginary  foreign  bodies  supposed  to  cause  many  diseases  were  also 
removed  by  sucking,  being  first  located  by  the  supernatural  \ision  of  the 
medicine-man — a  sort  of  roentgen-ray  eye,  as  it  were.  The  results  were 
made  more  tangible  by  previously  placing  something  in  the  mouth,  such  as  a 
stone,  thorn,  worm  or  insect,  and  producing  it  at  the  proper  psychologic 
moment. 

Numerous  ailments  were  held  to  be  due  to  the  presence  of  bile  in  the 
aflfected  part.  This  was  sucked  out  directly  with  the  mouth  or  through  a 
tube,  the  surgeon  apparently  expectorating  bile  frequently  during  the  pro- 
cess, being  enabled  to  do  so  by  chewing  a  species  of  yellow  root  in  prepara- 
tion for  the  occasion.  Such  procedures  were  of  course  nothing  but  blatant 
charlatanism,  but  they  had  a  certain  justification  in  the  psychologic  efi:'cct 
which  they  must  have  ]iroduced. 

Cupping. — This  was  a  common  remedy.  It  was  done  by  suction 
through  a  buffalo  horn  or  a  tube  of  wood  or  stone,  or  even  by  the  mouth 
alone.  Enough  force  could  thus  be  exerted  to  cause  much  congestion,  and 
an  expert  in  the  art  could  even  raise  a  blister.  W'et  cupping  was  achieved 
by  a  preliminary  sacrification  of  the  skin.  In  the  Museum  of  the  State  His- 
torical and  Natural  History  Society,  Denver,  are  some  peculiar  wooden 
instruments  from  the  Colorado  cliiif-dwe!lings,  labeled  "use  unknown," 
which  might  very  well  have  been  employed  for  cupping.  They  have  a  hole 
on  one  side  into  which  a  stem  could  be  inserted  to  suck  through,  the  body  of 
the  instrument  being  used  as  a  handle  to  press  it  firmly  against  the  skin 
(Fig.  SA). 

Scarification. — This  was  an  almost  uni\ersal  practice,  both  for  local 
troubles  and  those  of  a  more  general  nature.  It  was  often  done  with  a  flake 
of  flint,  although  more  elaborate  instruments  were  in  use,  ])rovided  with 
many  sharp  points  made  of  fish  spines,  flints,  etc.  A  method  employed  in 
Brazil  was  to  make  a  number  of  cuts  in  the  skin  through  which  was  inserted 
a  stone  instrument  like  a  spear  head,  which  was  moved  about  in  the  sub- 
cutaneous tissues — a  mode  cf  trc-.-ilnicul  that  could  nut  have  been  popular 
among  primitive  patients. 
Page  no 


LEONARD  FREEMAN 


Cauterization. — This  was  much  used.  It  was  acconipHshed  with  a  coal  of 
fire,  a  hot  stone,  or  by  burning  a  little  ball  of  cotton  or  other  inflammable 
substance  on  the  cutaneous  surface.  Among  other  things,  indolent  wounds 
and  ulcers  were  often  stimulated  by  cauterization,  and  it  was  also  employed 
as  a  counter  irritant  in  various  painful  affections.  A  favorite  method  was 
to  burn  tobacco  or  some  other  material  in  a  tube  made  of  stone  (Fig.  8R), 
and  then  blow  the  hot  smoke  through  the  tube  on  the  area  to  be  treated, 
decided  virtues  being  attributed  to  the  kind  of  smoke  employed. 

Phlebotomy. — This  was  extensively  used  in  the  treatment  of  local 
inflammation  as  well  as  many  general  diseases,  being  considered  almost  as 


Fig.  8.  .-/,  peculiar  wooden  instrument  with  cupped  end  (depth  not  well  shown) 
.ind  with  a  hole  on  one  side  slanted  upward,  into  which  a  hollow  reed  could  he 
inserted:  possihly  used  for  cupping,  by  pressing;  the  hollowed-out  end  against  the  skin, 
and  sucking  out  the  air  through  the  reed.  /V.  clilf  dweller's  stone  pipe,  also  used  for 
cupping  and  in  the  suction  treatment  of  abscesses  and  suppurating  wounds  (Museum 
of  State  Historical  and  Natural  History  Society,  Denver). 


much  of  a  cure-all  as  it  was  with  our  medical  forefathers.  The  vein  selected 
was  generally  in  the  leg  or  arm,  but  ncc;isionally  in  the  neck  or  temporal 
region.  The  instrument  emj)loye(I  in  opeiiing  the  vessel  was  made  from  a 
sharp  flake  of  flint  or  obsidian,  a  thorn,  :i  I'lsh  spine,  or  a  tooth  of  some  sort 
in  a  handle.  It  was  driven  with  a  quick  stroke  into  the  vein.  In  Brazil,  a 
little  arrow,  made  for  the  purpose,  was  shot  into  the  \ein  by  means  of  a 
diminutive  bow,  thus  coming  as  near  to  a  "shotgun  prescription"  as  was  pos- 
sible under  the  circumstances. 

Jiiflaiiinuilioiis. — These  were  lieaU-d  i-()i))i))iinly  by  poultices  ntade   iwnu 
plants,   leaves   or  barks    (slippery  elm,   etc.),  by   cupping,  and  by  counter- 


RA.VSOHOFF  MEMORIAL  VOLUME 


irritants,  sucli  as  the  cautery.  When  an  abscess  resulted,  incision  was  often 
resorted  to,  and  tlie  contents  were  aspirated  with  the  mouth,  directly  or 
through  a  tube. 

Amputation. — Although  not  extensively  jiracticed,  amputation  was  un- 
doubtedly done  at  times,  the  bleeding  being  checked,  perhaps,  by  the  appli- 
cation of  hot  stones,  as  has  been  observed  among  the  Indians.  .\n  image 
on  an  ancient  vase  found  in  Peru  distinctly  shows  the  stump  of  a  leg  due 
to  an  amputation. 

Hemorrhage. — The  use  of  the  tourniquet  was  undoubtedly  understood 
by  some,  but  the  more  common  method  of  checking  bleeding  was  by  the 
actual  cautery  (a  heated  stone)  or  by  local  pressure  aided  often  by  such 
coagulants  as  spiderwebs  and  the  fine  fibers  of  plants. 

Hernia. — Many  medicine-men  knew  how  to  hold  a  rupture  in  place  quite 
skilfully  with  various  forms  of  pads  and  bandages;  but  the  most  remarkable 
procedure  was  that  resorted  to  by  the  Pueblos,  who  treated  umbilical  hernia 


3 


Fig.  9.  Corset  made  oi  bark,  with 
liody;  possibly  used  for  some  ortbopedii 
Xatural  History  Society,  Denver). 


r   lacing   it   around   the 
if  State  Historical  and 


by  placing  on  it  a  number  of  large  black  ants,  the  bites  of  which  were  sup- 
posed to  have  a  curative  effect.  It  would  be  interesting  to  know  the  origm 
of  such  an  astonishing  idea. 

Pterygium. — Operations  for  pterygium  were  done  in  both  North  and 
South  America,  the  growth  being  more  or  less  skilfully  removed  with  shatp 
stone  knives.  It  was  probably  this  operation  that  gave  rise  to  the  erroneous 
idea  that  cataracts  w'ere  removed  by  these  ancient  ophthalmologists. 


LILONARD  FREEMAN 


Artificial  Skull  Deformities. — The  production  of  these  may  be  consid- 
ered as  a  sort  of  orthopedic  surgery*  extensively  practiced  by  various  North 
American  Indians,  as  well  as  those  of  Mexico  and  Peru.  Sometimes  a 
board  was  bound  against  the  forehead  of  an  infant  and  kept  there  during 
early  growth,  resulting  in  a  hideous  flatness  of  the  front  of  the  cranium 
(Flathead  Indians).  Other  tribes,  such  as  the  \'ancouvers,  Incas  and  Aztecs 
applied  pads  and  tight  bandages  to  the  head  in  such  ways  as  to  render  the 
skull  conical,  enormously  elongated,  or  deformed  in  other  monstrous  ways. 
Although  producing  an  outward  semblance  of  idiocy,  these  pecularities  of 
form  did  not  seem  in  any  way  to  influence  the  mentality.  Flattening  of  the 
occipital  region,  so  commonly  observed  in  collections  of  prehistoric  skulls, 
was  probably  more  or  less  accidental  and  due  to  pressure  of  the  infants' 
skulls  against  the  boards  on  which  they  were  habitually  strapped  and  carried. 

Anesthetics. — Although  it  cannot  be  questioned  that  some  of  our  primi- 
tive peoples  possessed  more  or  less  reliable  methods  of  anesthesia,  it  is  hardly 
probable  that  these  were  very  generally  known  or  employed.  For  instance, 
the  Zunis  and  some  other  tribes  used  for  the  purpose  of  substance  obtained 
from  the  jimson  weed  {Datura  metcloidcs) ,  containing  stramonium.  It 
was  administered  in  sufficient  amount  to  produce  indifference  to  pain  or 
even  complete  unconsciousness,  and  in  this  condition  abscesses  were  opened, 
fractures  set,  dislocations  reduced,  and  other  surgical  procedures  accom- 
plished. In  spile  of  heroic  dosage,  no  serious  harm  seemed  to  result.  It  is 
quite  possible  that  this  and  similar  methods  were  also  in  use  among  the 
Aztecs  and  Incas,  who  were  so  closely  related  in  many  ways  to  the  Pueblos. 

In  this  connection  should  not  be  overlooked  the  strong  hypnotic  influence 
imdoubtedly  exercised  by  the  medicine-men,  with  their  bizarre  make-U])S. 
weird  incantations,  and  fantastic  antics,  which  were  well  calculated  to  make 
a  profound  impression  on  their  credulous  patients. 

interesting  appliance  of  bark  made  to  fit  the  tor!>o  and  provided  with  eyrlcts  a';  thoiiKh  to  laic  it 
together  in  front  (Fig.  9).  It  closely  resembles  the  modern  orthopedic  corsets  used  in  the  tieatincnt 
of  lesions  of  the  spine,  and  may  have  been  used  by  the  Cliff  Dwellers  for  this  purpose  or  for  fracture 


WOLFF'S   LA\\'   AND   THE  FUNCTIONAL   PATHOGENESIS   OF 
DEFORMITY.* 

By  Albkrt  H.  Freiri:k(..   M.  D. 

Cincinnati. 

Tlie  C()rresi)ondencc  between  the  structure  of  bone,  under  normal  and 
abnormal  conditions,  and  the  calculation.s  of  graphic  statics  has  been  made 
tlie  foundation  upon  which  a  doctrine  of  "functional  pathogenesis"  has  been 
Isuilt.  It  has,  liowcver.  also  formed  the  basis  of  numerous  attacks  upon  this 
theory.  The  theory  of  the  functional  pathogenesis  of  deformity  and  that  of 
the  functional  shape  of  the  bones  have  been  made  corollaries  to  the  "law 
of  bone  transformation"^  by  its  author,  Jul.  Wolff.  The  "law  of  bone  trans- 
formation" is  considered  by  its  author  as  deriving  its  greatest  strength  from 
the  remarkable  resemblance  existing  between  the  internal  structure  of  the 
normal  human  femur  and  the  graphostatic  diagram  of  a  Fairbairn  crane 
drawn  by  the  niatliematician,  Cullmann.  This  was  given  an  outline  similar 
to  that  of  the  human  fennu-  deprived  of  its  trochanter  major  and  viewed  in 
coronal  section,  sustaining  a  load  of  30  kilogrammes.  This  load  is  supposed 
to  approximate  that  which  is  borne  by  the  femur  of  an  adult  and  to  be  ap- 
plied to  the  crane  in  a  manner  consistent  with  the  conditions  in  the  human 
subject.  The  striking  analogy  between  the  courses  of  the  bone  trabecuke 
in  the  frontal  section  of  the  femur  and  those  of  the  trajectories  of  Cullniann's 
diagram  was  first  insisted  upon  by  von  Meyer.  The  arrangement  of  the 
spongiosa  in  the  sagittal  section  of  the  femur,  corresponding  to  the  "neutral 
plane"  of  the  diagram,  was  foretold  by  Wolff  in  conformity  with  the  de- 
mands of  the  graphostatic  figure,  and  was  substantiated  by  him  later,  ana- 
tomically. After  the  most  painstaking  study  of  the  various  bones  of  the 
body  under  normal  and  abnormal  conditions  \\'olft"  was  able  to  formulate 
his  "law,"  which  might  be  translated  as  follows : 

"Every  change  in  the  form  and  function  of  the  bones,  or  of  their  func- 
tion alone,  is  followed  by  certain  definite  changes  in  their  internal  architec- 
ture, and  equally  definite  secondary  alterations  of  their  external  conforma- 
tion, in  accordance  with  mathematical  laws." 

Before  the  promulgation  of  Wolff's  law  the  generally  accepted  theory  of 
the  development  of  acquired  deformity  was  that  of  \'olkinann=-Hueter,'' 
namely,  that  consequent  upon  muscular  weakness  faulty  attitude  was  as- 
sumed, in  consequence  of  which  one  side  of  a  joint — c.  g.,  the  external  in 
genu  valgum — was  subjected  to  greater  pressure  than  normal ;  the  opposite 
side — the  internal  in  genu  valgum — sustained  less  pressure  than  normal. 
■Assuming  that  during  growth  the  normal  development  of  the  joint  depends 
uimn  the  maintenance  of  normal  conditions  of  inlra-articular  pressure,  it 
was  explained  that  the  increased  pressure  on  the  concave  side  interfered  with 


ALBERT  H.  FREIBERG 


the  normal  growth  of  bone  or  even  caused  atrophy  of  that  bone  already 
formed;  while  on  the  convex  (internal)  side  the  subnormal  pressure  per- 
mitted an  overgrowth  of  bone.  In  spite  of  the  fact  that  Mikulicz*  and 
Macewen^  showed,  quite  long  ago,  that  these  changes  in  the  articular  sur- 
faces and  epiphyses  are  not  constantly  present  in  genu  valgum,  but  that  the 
principal  deformity  exists  in  the  diaphyses  of  the  femur  and  tibia,  most 
authors  continued,  nevertheless,  to  describe  the  pathogenesis  of  this  deform- 
ity in  conformity  with  the  theory  of  Volkmann-Hueter.  ^^'e  shall  later  see 
how  it  is  better  explained  by  reference  to  Wolff's  law  and  in  agreement 
with  the  anatomical  conditions  present. 

The  first  corollary  which  Wolff's  theory  has  associated  with  it  is  that 
of  the  "functional  shape."'"'  The  external  form  and  internal  architecture  are 
determined  by  function  solely.  The  internal  architecture  and  external  con- 
tour always  correspond  exactly,  the  latter  representing,  mathematically, 
simply  the  last  curve  imiting  the  ends  of  the  various  trajectories  which  make 
up  the  internal  structure.  The  compact  substance  is  to  be  regarded  sinijily 
as  a  condetTsation  of  spongiosa. 

From  the  theory  of  the  "functional  shape"  it  is  an  easy  step  to  that  of 
the  "functional  pathogenesis"  of  deformity.  If  the  internal  structure  and 
external  contour  correspond  exactly,  and  if  they  represent  an  adaptation  to 
normal  function  only,  then  an  alteration  in  static  demands  made  upon  the 
bones  must  be  followed  by  the  proper  transformations  of  structure,  both 
internal  and  external,  and  as  the  result  of  these  we  have  the  "deformity  in 
the  narrower  sense."  The  deformity  is  therefore  to  be  regarded  as  a  physio- 
logical adaptation  of  structure  to  pathological  static  requirements,  therefore 
to  pathological  function. 

The  agreement  of  the  structure  of  bone,  both  under  normal  and  abnormal 
circumstances,  with  mathematical  laws,  and  in  particular  with  those  of 
graphic  statics,  is  insisted  upon  by  Wolff  to  such  an  extent  that  it  has 
formed  the  basis  of  attacks  upon  the  doctrine  by  Bahr'  and  Ghillini,*  as 
well  as  others.  It  is  their  object  to  show  that  Wolff's  mathematical  con- 
clusions are  erroneous,  and  that  therefore  it  is  not  permissible  to  make 
deductions  from  them  regarding  the  structure  of  the  bones  in  their  normal 
or  pathological  relations. 

We  may  well  ask  ourselves,  on  this  account,  whether  mathematical  proof 
of  the  competency  of  nature's  design  in  bone  structure  has  been  brought  bv 
Wolff  in  Cullmann's  drawing  of  the  Fairbairn  crane  and  the  deductions  fol- 
lowing. What  is  required  to  enable  us  to  construct  the  graphostatic  dia- 
gram of  the  femur?  It  must  be  understood,  as  a  preliminary  in  answering 
this  question,  that  when  "mathematical  proof"  is  spoken  of  mathematical 
accuracy  is  implied.  It  is  by  no  means  enough  to  say  that  a  striking  simi- 
larity exists  between  the  diagram  and  the  bone  whose  mechanics  we  are 
trying  to  solve.    There  must  be  absolutely  no  divergence  between  the  two. 


RAXSOHOFF  MEMORIAL  J-QLUME 


In  order  that  the  mechanics  of  the  femur  shall  be  submitted  to  mathe- 
matical proof,  we  must  know  every  possible  stress  to  which  the  bone  is  to  be 
submitted  under  normal  conditions,  and  these  stresses  must  be  expressed  in 
figures.  There  must  be  possible  of  expression  in  figures  the  physical  char- 
acteristics of  the  material  used  in  the  structure.  But  bones  are  evidently 
constructed  of  sufficient  strength  to  withstand  unusual  stress  without  giving 
way.  This  fact  is  demonstrated  in  every-day  life.  How  shall  we  calculate 
this  "factor  of  safety."  We  may  believe,  with  Wolff,  that  the  femur  is 
burdened  like  a  crane,  or  with  his  opponents  that  this  is  not  so ;  but  the  fact 
remains  that  Cullmann's  diagram  is  computed  without  mention  of  the  mus- 
cular stresses  upon  the  bone — without  reckoning  with  the  stresses  put  upon 
the  bones  in  other  positions  than  the  upright.  The  great  trochanter  has 
been  omitted  from  consideration  altogether.  This  is  obviously  not  per- 
missible in  a  mathematical  calculation,  because  it  is  always  present,  because 
it  is  the  means  of  transmitting  very  considerable  stress  to  the  femur,  and 
because  its  internal  structure  is  evidently  continuous  with  that  of  the  upper 
end  of  the  femur.  I  am  assured  by  experts  that  the  proper  calculation  of 
the  construction  of  the  femur  upon  exact  mathematical  lines  is  a  work  of 
great  magnitude,  requiring  not  only  uncommon  ability,  but,  on  account  of 
the  enormous  complexity  of  the  problem,  demanding  a  very  large  expendi- 
ture of  time.  To  my  knowledge,  no  such  exact  mathematical  demonstra- 
tion has  yet  been  made.  In  addition  to  this,  it  is  by  no  means  certain  that 
the  "factor  of  safety"  could  be  calculated;  this  factor  might  well  make  the 
mathematical  solution  impossible.  I'ntil  exact  mathematical  proof  is 
brought,  however,  there  would  seem  to  be  no  warrant  for  saying  thus 
definitely  that  the  external  contour  of  a  bone  represents  mathematically  the 
last  curve  uniting  the  ends  of  the  various  trajectories  which  make  up  the 
internal  structure — for  assuming  that  the  compact  substance  is  to  be  re- 
garded simply  as  a  consolidation  of  those  trajectories  coming  from  the 
spongiosa. 

If  we  are  unprepared,  however,  to  acknowledge  that  a  truly  mathemat- 
ical demonstration  of  the  structure  of  the  bones  has  been  made,  we  are,  on 
the  other  hand,  entirely  unwilling  to  reject  the  law  of  transformation  and  its 
corollaries  on  this  account  without  further  investigation.  In  declining  to 
accept  the  analogy  between  Cullmann's  diagram  and  the  structure  of  the 
femur  as  a  truly  mathematical  demonstration  of  the  latter,  we  are,  further- 
more, far  from  saying  that  if  such  computation  and  graphostatic  figure  were 
made  it  would  not  coincide  with  the  architecture  of  the  bone.  On  the  con- 
trary, the  structure  of  the  femur  having  been  shown  by  many  years  of 
observation  to  be  constant,  the  similarity  between  it  and  the  mathematical 
figure  is  so  striking  as  to  make  it  .seem  reasonably  certain  that  the  trabecule 
do  represent  lines  of  force  which  nature  aims  to  resist  by  the  laying  down  of 
the  bone  tissue.  This  is,  however,  far  from  being  mathematical  proof,  and, 
as  it  seems   to   us,  does   not  afford   justification   for  considering  some   of 

I'aiH-  IIU 


ALBERT  H.  FREIBERG 


Wolff's   other  conclusions  as   "matliematical."  however  true  they   may  be 
otherwise  shown  to  be. 

In  view  of  the  necessarily  great  variation  in  the  factors  of  weight- 
bearing  and  muscular  stresses  which  must  exist  in  mammals  other  than  man 
— because  of  the  deviation  from  the  erect  position  of  the  trunk  and  because 
of  the  participation  of  the  thoracic  extremeties  in  the  weight-bearing  func- 
tion, it  would  seem  likely  that  much  information  could  be  obtained  from 
the  study  of  their  bones.  Able  and  exhaustive  investigation  has  already  been 
made  in  this  direction  by  Zschokke,'"  Schmidt,"  and  others.  It  has  seemed 
worth  while  to  independently  repeat  some  of  this  work  as  well  as  to  .seek 
further  for  information  in  the  structure  of  other  mammalian  bones.  The 
femur  has  been  chosen  as  the  bone  for  further  comparison,  because  of  its 
size  and  static  importance  and  because  it  has  formed  the  basis  for  most  of 
the  conclusions  which  have  already  been  drawn.  In  examining  the  femora 
to  be  presently  described  the  method  reported  by  Wolff"  was  employed. 
Sections  were  cut  by  hand  by  means  of  a  saw.  These  sections  were  then 
photographed  by  means  of  the  Rontgen  ray,  and  from  the  negative  thus 
obtained  the  photographs  were  made  which  are  herewith  ])resented.  As  is 
the  case  with  many  radiographs,  the  negative  is  more  instructive  than  the 
print  made  from  it.  In  the  smaller  femora  it  was  C|uite  difficult  to  obtain 
prints  the  finer  details  of  which  would  lend  themselves  to  satisfactory  re])ro- 
duction. 

In  the  description  of  the  specimens  which  have  been  examined  care  has 
been  taken  to  avoid  as  much  as  possible  the  repetition  of  details  which  coin- 
cide with  the  descri[)tions  of  Zschokke  and  Schmidt,  above  referred  to.  The 
following  femora  have  been  examined  : 

I.     Ruminantia. 

(a)  Ox. 

(b)  Llama. 

(c)  Sheep. 

II.     Carnivora. 

(a)    South  African  leopard. 

III.     Primates. 

(a)    r.aboon  ( ]japio  hamadryas). 
(m)    Orang  (  simia  satyrus  ) . 
(c)   C.ibbon  (hylobates). 

(  Humerus  of  gibbon  also.) 

For  the  privilege  of  examining  into  the  architecture  of  the  femora  of 
the  orang  and  gibbon,  as  well  as  the  humerus  of  the  latter,  I  wish  to  acknowl- 
edge my  indebtedness  to  the  administration  of  the  Smithsonian  Institution. 
Many  of  the  other  bones  examined  have  been  taken  from  the  museum  of 
the  Cincinnati  Society  of  Natural  History. 


RAXSOHOFF  MEMORIAL  VOLUME 


REMARKS  OX  THE  SPECIMENS  EXAMINED. 
I.     RuMiNANTiA.     la)    Femur  of  the  Steer.     ^Fig.   1.) 

Relative  length  of  the  neck  is  short.  Capital  epiphysis  extends  laterally 
to  a  point  corresponding  practically  with  the  axis  of  the  shaft.  It  is  covered 
with  cartilage  to  this  point,  and  is  to  this  extent  a  hearing  surface.  The  angle 
made  by  the  neck  is  alxiut  112  lifsrrees. 


Fig.  1.     Femur  of  ynung  adult  steer. 

Arrangement  of  trabeculre  is  perfectly  constant,  and  corresponds  with 
the  description  of  Zschokke  and  Schmidt.  The  spongiosa  of  the  young 
adult  is  composed  of  exceedingly  fine  trabeculje.  As  the  age  increases  the 
trabecnlae  becomes  coarser  and  less  numerous,  so  that  the  internal  structure 
is  more  easily  read.  In  old  animals  this  change  has  continued,  so  that  the 
difference  between  their  spongiosa  and  that  of  the  young  animal  is  most 
striking  (see  Zschokke).  The  three  most  striking  systems  of  trabeculas 
seen  are : 

1.  Principal  pressure  trajectories  (converging  from  the  mesial  part  of 
the  head  to  the  adductor  compacta). 

2.  Trabeculje  from  adductor  and  abductor  compacta  arch  toward  the 
axis  of  the  bones,  forming  a  series  of  gothic  arches  whose  apices  are  in  a 
straight  line  with  the  lateral  boundary  of  the  capital  epiphysis.  Such  a 
series  of  arches  also  exists  in  the  trochanteric  epiphysis.  Orthogonal  cross- 
ings can  be  distinguished  in  the  system  of  arches. 

(b)   I'eniur  of  the  Llama.      (Fig.  2.\ 

There  is  practically  no  neck  to  the  bone.  Ca])ital  ej^iphysis  extends  to 
the  axis  of  the  shaft,  as  in  the  steer,  but  the  head  is  set  more  obliquely, 
making  an  angle  of  120  degrees  with  the  shaft. 

Although  the  animal  is  comparatively  young  (shown  by  imperfect  union 
of  epiphysis),  the  trabeculae  are  comparatively  coarse,  their  meshes  large. 
The  arrangement  of  gothic  arches  is  lacking. 

The  marrow  cavity  extends  comparatively  high  into  the  U])])er  end  of  the 
bone.    There  are  three  systems  of  trabeculae  : 

Page  n& 


ALBERT  H.  FREIBERG 


^.. 


Fig.  2.     Femur  of  Llama. 

1.  Principal  pressure  trabeculas. 

2.  Two  systems  diverging  from  tlie  base  of  the  great  troclianler. 

(a)  Toward  the  head. 

(b)  Downward  to  the  al)duclor  compaota. 

(<■)  /•■<•»/»;■  of  the  Slu-if.     (  I'ig.  X) 
In  general  shape  and  ])lan  of  internal  structure  we  have  tlie  steer's  femur 
in  miniature.     The  angle  of  the  neck  is  somewhat  greater  (115  degrees  to 


Fig.  3.     Sheep. 
117  degrees),  otherwise  the  same  arrangement  of  capital  epiphysis  and  golhic 
arches,  though  sometimes  not  so  easily  made  out.    (  Jrthogonal  crossings  can 
in  part  be  distinguished. 

II.     Caknivora.      (I'ig.  4.) 
The  only  specimen  examined  was  the  femur  of  a  South  African  len]iard. 
The  femur  is  characterized  by  its  pro])ortionalely  long,  slender,  .and  some- 
what curved  neck,  which  makes  an  angle  of    130  degrees   with  the   shaft. 
The  spongiosa  is  made  of  plates. 


RAXSOHUFF  MFMORIAL  VOLUME 


The  femoral  neck  presents  a  triangular  cavity  of  considerable  size, 
and  which  in  position  and  boundaries  would  correspond  with  Ward's  tri- 
angle of  the  human  femur.  This  is  separated  from  the  marrow  cavity  below 
bv  a  small  number  of  arches  coming  from  the  adductor  compacta  and  corre- 
sponding to  pressure  trajectories.    The  crossings  here  are  orthogonal. 

Shorn  of  the  trochanter  major  the  outline  is  very  like  that  of  Cullniann'> 
diagram;  the  internal  arrangement  is,  however,  very  different. 

III.     Prim.mf.s.     (a)   Femur  of  Arabian  Baboon    (Pafio  Hainadryas.)      (Fig.  5.) 
The  bone  is  remarkably  heavy  for  its  size,  and  of  very  dense  texture, 
so  that  it  is  difficult  to  saw.     Tlie  neck  is  curved,  and  makes  an  angle  of 
about  124  degrees. 


Baboon. 


The  trabeculae  are  massive,  largely  in  the  form  of  plates.  In  the  head 
they  are  fairly  typical  as  principal  pressure  trabeculse,  and  here  show  ortho- 
gonal crossings,  with  a  few  tension  plates.  There  is  here,  too,  a  cavity  in 
the  neck,  separated  by  a  few  plates  only  from  the  cavity  of  the  shaft  below. 
The  compacta  of  the  shaft  is  relatively  very  heavy  and  thick,  so  that  it  is 
difficult  to  bring  it  into  comparison  with  the  amount  of  spongiosa. 


ALBERT  H.  FREIBERG 


(b)    Orang.      (Fig.  6.) 

Both  in  external  conformation  and  internal  structure  the  upper  femoral 
end  is  strikingly  like  tiie  human.  The  angle  made  by  the  femoral  neck  is 
135  degrees.  Both  pressure  and  tension  trajectories  are  found  projected  in 
a  fairly  typical  manner,  though  the  reticulum  is  much  coarser  than  in  man. 


the  trabeculae  more  plate-like.  Orthogonal  crossings  can  be  made  out  to  a 
limited  extent.  The  condensation  of  spongiosa  known  as  the  "intermediary 
epiphyseal  disk"  (Recklinghausen),  and  which  is  constant  in  the  adult 
femur,  is  lacking. 

In  general  outline  the  upper  femoral  end  greatly  resembles  that  of  the 
orang  and  man.     The  bone   is   remarkably   light,   however,   its  shaft  very 


Fig.  7.    Femur  of  gibbon. 


smooth  and  round,  reminding  one  very  forcibly  of  the  bones  of  larger  birds. 
This  coiuparison  seems  all  the  more  apt  upon  bisecting  the  bone,  because  of 
the  relatively  large  marrow  cavity,  with  no  spongy  structure  whatever  save 
at  the  extreme  ends.    The  angle  of  the  neck  is  140  degrees. 


RANSOM  OFF  MFMORIAL  VOLUME 


The  section  shows  a  spongiosa  of  lamellar  character,  in  which  it  is 
extremely  difficult,  if  at  all  possible,  to  find  an  arrangement  in  any  way 
similar  to  that  of  man  or,  indeed,  of  any  of  the  femora  previously  described. 
The  neck  i)roper  is  practically  free  from  spongy  structure,  a  cavity  being 
here  found  which  extends  to  the  spongiosa  of  the  head  above  and  to  that 
at  the  base  of  the  great  trochanter  below.  The  cellular  spaces  of  the 
spongiosa  are  relatively  very  large. 

In  view  of  the  contrast  in  functional  importance  between  the  femur  and 
the  humerus  in  the  gibbon,  great  interest  must  attend  the  comparison  of 
their  internal  structures.  The  result  of  it  is  in  accord  with  our  anticipa- 
tion. The  internal  structure  consists  of  a  lamellar  spongiosa  of  compara- 
tively coarse  mesh,  but  in  its  general  arrangement  strikingly  that  of  the 
human  humerus.  This  is  true  even  to  the  existence  of  a  place  near  the  great 
tuberosity  in  which  the  spongiosa  is  quite  rare,  almost  to  the  degree  of  being 
considered  a  cavity.  The  remains  of  the  epiphyseal  line  correspond  both  in 
direction  and  position,  and  the  outline  is  simply  a  miniature  of  the  human. 
(Fig.  8.) 

In  addition,  it  is  to  be  noted  that  the  gibbon's  humerus  is,  in  comparison 
with  its  femur,  heavier  and  denser.  On  holding  the  bones  close  to  a  bright 
light  the  shaft  of  the  femur  is  seen  to  be  quite  translucent ;  that  of  the 
humerus  is  not  at  all  so.  While  the  humerus  is  a  longer  bone,  its  density  is 
disproportionately  greater  than  that  of  the  femur.  The  volume  of  the  two 
bones  was  determined  by  ascertaining  their  displacement  of  water.  This 
was  found  to  be  25  cc.  for  the  humerus  and  22  cc.  for  the  femur.  The 
weight  of  the  humerus  was  30.45  grammes  against  21.67  grammes  for  the 
femur.  Their  ratio  of  weight  is  therefore  1.405,  while  their  ratio  of  volume 
is  1.045.  It  is  easily  seen  that  the  humerus  is  an  organ  of  greater  strength 
and  usefulness  than  the  femur. 

In  making  a  general  comparison  of  the  specimens  in  hand,  it  is  well  to 
remember  that  in  graphic  statics : 

1.  The  courses  of  the  various  trajectories  are  dependent  upon  the  exter- 
nal shape  of  the  structures,  and  conversely, 

2.  The  number  of  the  trajectories  and  their  size  depend  upon  the  vary- 
ing factors  of  weight  and  the  character  of  the  material. 

It  was  remarked  by  Zschokke — and  the  statement  is  to  day  equally  true- 
that  it  was  not  possible  to  estimate  the  stresses  in  bone  more  than  approxi- 
mately up  to  that  time,  but  that  it  was  necessary  as  a  matter  of  scientific 
reasoning  to  show,  at  least  in  some  bones,  that  the  trabeculas  truly  corre- 
.spond  to  the  trajectories  in  direction  and  strength.  Ten  years  have  elapsed 
since  this  was  written,  but  the  task  has  not  yet  been  performed. 

Bahr.  Ghillini,  and  the  latter  in  co-operation  with  Canevazzi,  have  offered 
certain  calculations  in  opposition,  but  these  by  no  means  present  the  solu- 
tion which  we  seek.  It  would  appear,  therefore,  that  we  are  not  yet  pro- 
vided  with   exact   data   to   attempt    a   truly   mathematical   solution    of   the 

Page  tZZ 


ALBERT  H.   FREIBERG 


mechanics  of  the  femur.  If  we  cling  too  closely  to  the  mathematical  con- 
cept of  bone  structure  we  shall  find  it  impossible,  for  example,  to  reconcile 
the  structures  in  the  upper  femoral  ends  of  the  gibbon  and  the  orang.  We 
have  here  a  striking  similarity  of  outline,  with  an  equally  marked  incon- 
gruity of  internal  formation. 

If,  however,  we  depart  from  the  strictly  mathematical  notion  and  exam- 
ine into  the  environment  and  habits  of  the  gibbon  and  orang  we  shall  find  an 
admirable  adaptation  of  structure  to  these  and  an  explanation  of  the  great 
variation  in  internal  structure.  According  to  Flower  and  Lydekker,*  the 
gibbon  is  by  nature  an  arboreal  creature  of  great  lightness,  accustomed  to 
maintain  itself  almost  entirely  by  the  thoracic  extremities.  Its  movements 
are  extremely  rapid,  and  it  is  able  to  project  its  body  through  long  distances 
in  space  in  swinging  from  bough  to  bough  and  from  tree  to  tree.  When 
pursued  on  the  ground  and  unable  to  reach  a  tree  it  moves  forward  chiefly 
on  its  pelvic  extremeties,  and  practically  in  the  upright  position,  but  so 
awkwardly  and  uncertainly  that  it  is  easily  overtaken  by  man.  The  humerus 
of  the  gibbon,  however,  belongs  to  the  extremity  of  greater  power  and  use, 
and  is  manifestly  of  corresponding  build.  In  the  orang,  on  the  other  hand, 
we  find  great  muscular  power  in  the  posterior  extremities  and  comparative 
slowness  in  movement.  We  may  similarly  compare  the  femora  of  the 
leopard  and  the  baboon,  although  possibly  not  so  aptly,  the  former  possess- 
ing wonderful  agility  and  ability  to  make  enormous  leaps,  the  latter  being 
contrasted  by  the  great  muscular  development  in  proportion  to  its  size.  Ac- 
cording to  Zschokke,  the  femora  of  bears  able  and  accustomed  to  maintain 
themselves  frequently  in  the  upright  position  possess  great  resemblance  to  the 
human  in  their  structure.  So  in  the  ruminants,  also,  we  find  the  modifica- 
tions of  internal  structure  in  accordance  with  the  shortness  of  the  femoral 
neck,  adapted,  as  this  is,  to  weight-bearing  purely  rather  than  a  large  range 
of  motion. 

From  the  above  we  should  be  justified  in  concluding  that  while  external 
conformation  and  internal  structure  represent  admirable  adaptation  to  use, 
their  mutual  interdependence  is  not  so  exact  as  the  strictly  mathematical 
concept  would  require.  If  we  are  to  modify  the  doctrine  of  the  functional 
shape  of  the  bones  to  this  extent,  it  is  probable  that  the  doctrine  of  func- 
tional pathogenesis  must  likewise  be  qualified. 

Valuable  evidence  for  the  theory  of  functional  pathogenesis  should  be 
found  where  the  function  of  a  bone  has  been  changed  for  a  considerable  time 
without  any  gross  solution  of  its  continuity.  It  is  believed  that  such  evidence 
can  be  found  in  the  specimen  of  old  unreduced  dislocation  of  the  hip  which 
is  next  presented,  and  in  which  we  have  the  advantage  of  comparison  with 
the  normal  femur  of  the  same  individual. 


RAXSOHOFF  MFMOKIAL  I'OLVME 


Description  of  Specimen  of  Old  Unreduced  Dislocation  of  the  Hif.  from  the 
Museum  of  the  Cincinnati  Hospital  (Series  I'll,  No.  127  /). 

The  specimen  has  been  in  the  museum  for  many  years,  and  all  clue  to 
the  history  of  the  case  has  been  lost.     The  board  has  wired  upon  it: 

The  Os  Innominatum  of  the  Side  of  the  Luxation.  This  shows  the 
acetabulum  to  have  been  unoccupied  by  the  femoral  head  for  a  long  time. 
The  floor  has  become  roughened  by  the  presence  of  small  osteophytes.  The 
acetabular  cavity  appears  to  have  become  smaller  by  the  thickening  of  its  rim 
and  the  formation  of  new  bone  in  its  floor.  Just  behind  the  acetabulum 
there  is  seen  a  rather  flat,  though  slightly  concave,  bone  mass  of  roundish 
outline,  with  a  diameter  of  5  to  3.5  cm.,  and  elevated  0.52  to  0.53  cm.  above 
the  surface  of  the  surrounding  bone.     This  rests  upon  a  buttress  of  bone 


thrown  out  from  the  ilium  and  ischium.  It  is  evidently  the  representation  of 
an  attempt  at  forming  a  new  acetabulum. 

The  Upper  Hnd  of  the  Right  (Dislocated)  Femur.  (Fig.  9.)  This  has 
been  sawed  through  about  8  cm.  below  the  tip  of  the  great  trochanter.  It 
has  also  been  bisected  in  coronal  section. 

The  Upper  End  of  the  Left  Femur  (Normal).  (Fig.  10.)  This  has  been 
sawed  through  at  6.7  cm.  below  the  tip  of  the  great  trochanter,  the  cut  just 
striking  the  tip  of  the  lesser  trochanter.  It  has  also  been  bisected  in  coronal 
section.  Upon  joining  the  halves  of  the  right  (luxated)  femur  and  attempt- 
ing to  fit  the  head,  in  its  dislocated  position,  into  the  new  acetabulum,  it  is 
readily  seen  that  its  superior  surface — that  which  formerly  was  the  chief 
means  of  transmitting  weight — was  no  longer  a  bearing  surface,  but  that  the 
joint  bearing  under  the  new  conditions  was  displaced  downward.     It  can  be 


ALBERT  H.  FREIBERG 


seen  that  the  position  of  the  femur  could  not  have  been  maintained  by  the 
bony  socket  alone,  but  that  the  soft  parts  must  have  played  an  important  if 
not  the  chief  role  in  this. 

The  examination  of  the  femoral  head  shows  at  once  that  it  may  be 
divided,  functionalh-.  into  an  anterior  and  posterior,  an  upper  and  lower 
segment.  The  anteri(jr  segment  is  characterized  b)-  the  smoothness  of  its 
external  contour  and  its  roundness  when  compared  with  the  posterior  seg- 
ment, w'hich  is  rough,  presenting  irregular  elevations.  The  margin  of  the 
head  in  the  posterior  segment  is  considerably  mushroomed ;  this  is  not  so 
in  the  anterior.  The  corticalis  of  the  posterior  segment  is  very  thin,  and  in 
one  place  has  disappeared,  so  that  the  spongiosa  is  exposed.  (This  is  not 
broken.)     The  head  is  no  longer  nearly  spherical,  but  bullet-shaped,  with  a 


\ 


Fig.  10.     Xnrnial   femur   from  same  subject. 

rounded  apex  in  the  line  of  the  cervical  axis.  Crossing  the  anterior  seg- 
ment is  a  slight  ridge  which  divides  the  anterior  segment  into  an  upper 
and  lower  portion.  The  upper  portion  is  somewhat  rougher  and  flatter  than 
the  lower,  and  this  division  will  be  later  referred  to  in  the  description  of  the 
section. 

From  the  anterior  half  of  this  femur  a  section  was  cut  varying  from 
3  to  4  mm.  in  thickness.  A  similar  section  was  taken  from  the  left  femur. 
Through  a  mishap  the  spongy  portion  in  the  lower  portion  of  this  section 
was  broken.  The  spongy  tissue  should  be  intact  through  the  section.  The 
following  measurements  show  in  part  the  decided  differences  existing  be- 
tween the  right  and  left  femurs:  Diameter  from  the  circumference  of  the 
head  to  the  base  of  trochanter  major:  right,  8:75  cm.;  left,  10.40  cm. 
Height  of  trochanter  major  from  tip  to  base:  right,  4  cm.;  left,  4.46  cm. 
Cireatest  thickness  of  adductor  compacla :  right,  0.58  cm.;  left,  0.44  cm. 
Greatest  thickness  of  abductor  compacta :  right,  0.57  cm.;  left,  0.34  cm. 
Angle  betw-een  the  neck  and  shaft:  right,  122  degrees;  left,  127  degrees. 

Page  ].a 


RANSOHOFF  MEMORIAL  VOLUME 


The  following  changes  of  external  configuration  may  therefore  be  noted : 
(a)  General  diminution  in  the  size  of  the  bone;  (b)  diminution  of  the  angle 
between  the  shaft  and  the  neck;  (c)  alterations  in  the  shape  of  the  femoral 
head,  as  before  described. 

The  transmutations  of  the  internal  structure  are.  however,  more  strik- 
ing, and  when  taken  in  conjunction  with  the  above-mentioned  alterations  of 
external  contour,  and  in  view  of  the  changed  conditions  of  stress  from  both 
weight-bearing  and  muscular  action,  make  it  possible  for  us  to  present  a 
rational  interpretation.    These  transmutations  may  be  described  as  follows : 

1.  The  cancellous  tissue  is  of  looser  mesh  than  that  of  the  left  femur. 

2.  The  tension  trabeculse  proceeding  from  the  abductor  side  are  shorter 
in  length,  but  also  of  changed  (shortened)  radii.  The  pressure  trabecule, 
however,  seem,  if  anything,  more  numerous  and  of  greater  strength  than 
those  of  the  left  femur.  As  the  result  of  this.  Ward's  triangle,  which  is 
ordinarily  constituted  by  the  convergence  of  two  well-defined  groups  of 
trabeculae  coming  from  the  upper  part  of  the  head  and  region  of  the  great 
trochanter,  respectively,  has  disappeared  entirely. 

3.  The  most  conspicuous  change  of  the  internal  composition  is,  however, 
to  be  observed  in  the  head.  We  have  here  a  considerable  cavity  in  the 
spongy  tissue,  corresponding  in  position  to  the  flattened  part  of  the  head, 
and  which  is  traversed  by  a  few  bone  plates.  The  antero-posterior  depth  of 
this  cavity  is  2.50  cm.;  its  width  in  the  coronal  section  is  2  cm.  The 
antero-posterior  diameter  of  the  head  at  this  part  is  3.40  cm.  The  floor  of 
this  cavity  corresponds  exactly  with  that  ridge  on  the  anterior  aspect  of  the 
head  which  divides  this  into  an  upper  and  lower  segment. 

4.  I']ion  examining  the  anterior  and  posterior  halves  of  the  l)one,  it  is 
seen  that  the  cancellous  arrangement  in  the  anterior  segment  is  more  com 
pact. 

I'nfortunate  as  it  is  for  the  present  inquiry  that  no  record  is  left  to 
siiow  the  exact  amount  of  motion  and  strength  possessed  by  this  dislocated 
hip,  the  changes  of  its  structure  nevertheless  correspond  strikingly  with  the 
requirements  of  Wolff's  law.  The  atrophy  of  the  unused  parts,  and  the 
condensation  of  those  bearing  increased  stress,  as  well  as  the  decided  change 
of  external  conformation,  are  sufficiently  manifest  as  to  impossibly  escape 
notice.  Equally  evident,  however,  are  the  encroachment  upon  the  original 
size  of  the  acetabular  cavity  by  the  formation  of  new  bone,  and  the  irregular 
surface  of  the  unused  part  of  the  femoral  head  for  the  same  reason.  I  take 
it  that  we  have  here  conditions  analogous  to  the  so-called  hypertrophy  of 
the  inner  condyle  in  genu  valgum,  and  that  we  are  dealing  with  an  increase 
in  cubical  dimensions  as  an  accommodation  to  altered  conditions  of  space. 
If  this  increase  of  cubical  dimensions  is  to  be  so  regarded  it  must  be  looked 
upon  as  a  result  of  the  deformity  and  not  as  one  of  its  causes,  lis  functional 
role  in  resisting  stress  can.  fnun  it>  physical  characters,  be  considered  insig- 
nificant. 


ALDTiRT  H.  FREIBERG 


From  the  researches  of  Wolff,  Zchokke,  Schmidt,  and  others,  as  well 
as  from  the  observations  herewith  presented,  it  is  believed  justiliable  to  con- 
clude as  follows : 

1.  The  strictly  mathematical  concept  of  Wolff's  law  has  not  yet  been 
justified  by  demonstration. 

2.  vSave  in  their  mathematical  aspects,  the  statenienls  of  Wolff's  law 
and  its  corollaries  may  be  accepted  as  being  in  agreement  with  observations 
hitherto  made. 

3.  If  we  accept  the  foregoing  statements  it  does  not  follow  that  we 
must  make  use  of  the  so-called  "functional  methods"  in  our  therapeutic 
endeavors ;  they  are  to  be  chosen  not  for  theoretical  considerations  only,  but 
for  reasons  of  expediency  and  practicability. 

[Note. — In  the  discussion  following  the  reading  of  this  paper  there  was 
presented  the  right  femur  of  an  idiotic  woman,  thirty-five  years  of  age,  by 
Dr.  R.  Tunstall  Taylor,  of  Baltimore.  The  specimen  is  of  such  interest,  and 
is  believed  to  be  corroborative  to  such  a  degree,  that,  with  Dr.  Taylor's  kind 
permission,  the  case  and  section  of  the  bone  are  herewith  briefly  presented. 
The  subject  from  whom  it  came  was  a  paralytic,  considerably  deformed, 
having  severe  scoliosis  and  being  greatly  underdeveloped.  The  fibula  of  this 
subject  was  about  15  inches  long  and  somewhat  greater  in  thickness  than  a 
good-sized  knitting  needle.  The  pelvis  was  likewise  deformed.  The  femur 
is  extremely  light  in  weight.  Its  extreme  length  is  38  cm. ;  the  coronal 
diameter  of  the  shaft  at  the  middle  is  1.3  cm.  The  head  is  greatly  flattened 
from  above  downward,  as  may  be  seen  from  the  section.  The  surface  is 
marked  by  several  deep  groo\es  of  antero-posterior  direction.  Otherwise 
the  bone  is  of  fairly  normal  shape,  with  the  exception  of  the  trochanter 
minor,  which  forms  a  quite  long  spur  projecting  anteriorly,  leaving  a  deep 
groove  between  it  and  the  upper  part  of  the  sliaft.  The  radiogram  of  the 
section  of   the   upper  extremity   of   this   femur   is   almost   self-explanatory. 


/ 


if  femoral  head  o 

i  a  paralvtic  idiot 

,  awed 

(By   permission 

of  Dr.  R.  T.  Tay 

lor.) 

Section 


(Fig.  11.)  \'estiges  of  the  normal  internal  struclurc  arc  a]»parent.  Such  are 
the  intermediary  epiphyseal  disk,  some  of  the  princijjal  pressure  trajec- 
tories, and  some  of  the  arches  as  well.  The  upper  end  of  the  bone  is,  how- 
ever, merely  a  hollow  shell,  and  expressive,  it  seems  to  me,  not  only  of  imper- 

Pagc  in 


RAXSOHOFf  MfiMORIAL  VOLUME 


feet  development,  but  of  general  atrophv  also.    As  tar  as  can  be  ascertained, 
this  person  was  never  able  to  maintain  the  upright  position.] 


Wolff. 

Gesftz.  d. 

Transformation  d.  Kochcn. 

Berlin. 

1892. 

Volkm.-,nn.  v.     Pil 

iha  11.   Billroih-s  Chinircie.  i 

i.,  Ahth 

.   IJ. 

p.   693 

ct 

scq. 

Mufter 

.     Virrhow 

■s   Arrhiv.    XXV.    p.    S72   et   «p 

a. 

Mikulii 
Jfacew; 

:z.      Arch, 
an.     Lancel 

f.   klin.    Chir.,   xxiii.    p.    561 
t,    Septemhcr.    1884. 

Wolff. 

Loc.   cit.. 

p.  sn. 

Rahr. 

Zcit=cl,r.   f 

.   Orth,   Cliir..   V.   p.  52.  295; 

;  Band. 

p.   522. 

Chillin; 

i.      Zeit=chr 

.    f.    Orth.    Chir..    VI.    p.    589: 

;   ix,   p. 

178. 

Wolff. 

Berl.    klin 

.    Wochenschr,,    1900,   No.    18. 

Zschokke.        Weite 

re     I-ntersuchuneen     ueber 

das     \- 

d. 

Kn 

Schmidt.      Zeitschi 

r.   f.   Wisscnsch.      Zodlogie. 

Ixv.    p. 

65   e 

t  seq. 

Wolff. 

Arch.   f.   1 

klin.   Chir..   Band  liii.   Heft 

Wolff. 

T-phpt  d. 

Wech-^plheziehunEen   zw.   d. 

Form  u   .d. 

Functi 

on 

d.  e 

nus.   I.e 

ipzis.   1901. 

zetnen   Gebilde  d. 


THE  ATROPIN  TEST  IN  THE  DIAGNOSIS  OF  TYPHOID 
INFECTIONS.* 

Aij'RED   FkiI'Dlander,   M.  D.    (Cincinnati) 

and 

Cakicv  p.  :\IcCord,  M.D.  (Detroit) 

Chiefs    of   Medical    and    of   Laboratory    Strviro.    respcclivcly, 
Base   Hospital 

Camp  Sherman,  Chillicothe,  Ohio 

With  all  appreciation  of  the  minimizing  effect  of  typhoid-paratyphoid 
prophylaxis  on  typhoid  infections  in  army  camps,  it  is  still  reasonable  to 
anticipate  the  occurrence  of  occasional  camp  cases.  The  larger  numljer  of 
such  cases  will  probably  arise  from  among  unvaccinated  civilian  wurkmen 
and  from  the  improperly  vaccinated  soldier.  In  typhoid  infections  ap])earing 
in  persons  who  have  received  typhoid  prophylaxis  completely  or  incompletely, 
the  disease  will  usually  be  characterized  by  such  mildness  as  not  to  present 
the  outstanding  features  of  typhoid  that  so  readily  permit  a  diagnosis  among 
the  unvaccinated.  Facing  this  difficulty  in  the  recognition  of  typhoid  exist- 
ence, those  medical  officers  responsible  for  the  prevention  of  infectious 
diseases  in  army  camps,  and  those  on  whom  will  devolve  the  care  and  treat- 
ment of  suspected  cases,  are  evaluating  all  recent  developments  purporting 
to  be  of  additional  diagnostic  aid.  At  a  similar  period  in  the  making  of  the 
British  Army  there  came  into  use  the  atropin  test  as  a  means  for  the  detec- 
tion of  typhoid  infections.  The  British  Medical  Research  Committee  has 
sanctioned  this  test's  reliability  to  the  extent  of  issuing  a  monograph  on  the 
subject,  prepared  by  Marris.' 

In  this  hospital  up  to  the  present  time  no  cases  of  typhoid  have  occurred; 
but  in  order  to  be  conversant  with  the  merits  and  technic  of  the  atropin  test 
against  the  contingency  of  typhoid  outbreak,  228  cases  of  diverse  diseases 
other  than  typhoid  and  paratyphoid  have  been  tested  in  the  manner  described 
by  Marris.    The  results  form  the  basis  of  this  report. 

THE  KATIOXALE  AND  TECHXIC  OF  THE  ATROPIX  TEST. 
According  to  the  sponsors  of  this  test,  the  normal  individual  or  the  patient 
ill  of  diseases  other  than  typhoid  infections  responds  to  the  administration 
of  atropin  with  a  noteworthy  increase  in  heart  rate.  In  typhoid  patients, 
however,  this  acceleration  either  does  not  occur  or  occurs  to  a  lessened 
degree.  This  difference  is  attributed  to  an  antagonism  of  action  between 
the  alkaloid  and  the  toxins  produced  by  the  organisms  of  the  typhoid  group. 
This  relative  lack  of  response  to  atropin  is  the  basis  of  the  test,  the  applica- 
tion of  which  is  as  now  noted: 

The  patient  Hes  horizontally  and  is  instructed  to  remain  completely  at  rest  through- 
out this  test,  which  is  not  employed  until  at  least  one  hour  has  elapsed  from  the  last 
meal.     The  pulse  rate  is  counted  minute  by  minute  until  it  is  found  to  be  steady ;  ten 

Troni  The   Journal   of  tlie    .\i 

1.     Marris,   F.   A.:     Use  of  A' 

Infections,   Brit,   Med.  Jour.,   1910, 


RAXSOIWFF  MEMORIAL  VOLUME 


minutes  of  such  counting  usually  suffices.  Atrophin  sulphate  is  then  injected  hypoderm- 
ically  in  the  dose  of  1/3^  grain,  preferably  over  the  triceps  region  to  insure  rapid 
absorption.  An  internal  of  twenty-five  minutes  is  allowed  to  elapse,  and  the  pulse  rate 
is  again  counted,  minute  by  minute,  until  it  is  clear  that  any  rise  which  may  follow  the 
injection  has  passed  off;  fifteen  or  twenty  minutes  may  be  necessary  for  this  purpose 
when  the  pulse  rate  is  raised  at  the  first  count. 

If,  for  example,  a  near  constant  pulse  rate  of  70  was  exhibited  at  the 
preliminary  counting,  and  a  maximum  of  96  was  exhibited  at  the  pulse  rate 
subsequent  to  atropin  injection,  the  inference  after  this  acceleration  of 
twenty-six  heats  per  minute  would,  under  the  provisions  of  the  test,  be  that 
the  condition  was  not  typhoid.  If,  however,  the  rate  after  atropin  had 
attained  only  to  78  beats  per  minute  as  the  maximum,  the  inference  is  tena- 
ble that  the  existing  condition  is  one  of  the  typhoid  group.  The  test  does  not 
discriminate  between  typhoid  and  paratyphoids  A  and  E.  In  Marris' 
report,  the  line  of  demarcation  for  the  interpretation  as  existing  typhoid  or 
nontyphoid  is  placed  at  fifteen  ;  that  is.  if  the  acceleration  following  atropin 
is  less  than  fifteen  beats  per  minute,  typhoid  is  indicated;  if  the  increase  is 
fifteen  or  more  per  minutes,  typhoid  is  not  indicated.  A  "positive"  atropin 
reaction  is  one  giving  rise  to  little  or  no  increased  heart  rate  after  atropin 
administration  (  fourteen  or  less  per  minutel.  A  "negative"  reaction  is  one 
giving  rise  to  an  increase  of  fifteen  or  greater. 

If  the  patient  is  admitted  during  the  first  fortnight  of  his  illness,  the  test  is  applied 
as  soon  as  possible  after  admission  and  is  charted  with  the  temperature.  When  a  posi- 
tive reaction  (little  or  no  response  to  atropin)  is  obtained,  the  diagnosis  of  infection 
with  a  member  of  the  enteric  group  of  organisms  may  be  made.  In  the  case  of  a  nega- 
tive reaction,  the  test  should  be  repeated  after  two  or  three  days,  and  if  again  negative, 
it  is  again  repeated.  Three  negative  reactions  falling  within  the  first  fortnight  of  the 
illness  exclude  the  presence  of  typhoid  with  a  considerable  degree  of  certainty :  there 
are  rare  exceptions,  and  in  these  a  continuation  of  the  test  is  usually  suggested  by  the 
symptoms  and  remaining  clinical  signs. 


4|,|.|3| 

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■"■^ 

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Chart  1.  Typical  positive  atropin  test  in  measles  patient  presenting  clinical  mani- 
festation similar  to  those  of  the  patient  whose  reaction  is  shown  in  Chart  2.  The 
broken  line  after  the  administration  of  the  atropin  represents  an  interval  of  twenty- 
five  minutes. 


In  the  normal  individual  to  whom  has  been  administered  1  30  or  1/33 
grain  of  atropin,  some  or  all  of  the  following  manifestations  may  be  expected 
to  occur:  A  slight  and  transient  decrease  of  the  pulse  rate  (two  or  four 
beats  per  minute)  occurs  early  with  a  return  to  normal.  This  is  followed 
by  a  rapid  increase  in  heart  rate  of  from  twenty  to  thirty-five  beats.  The 
height  of  this  acceleration  is  reached  in  about  one-half  hour,  slowly  returning 
to  normal  in  one  or  two  hours.  The  classical  characteristics  of  atropin  action, 
lessened   secretions  and   dilated   pupils,   seldom  are  observable   during  the 

Page  IM 


ALFRED  FRIRDLAXDRR  AND  CAREY  P.  McCORD 

testing  period,  but  at  times  may  be  noted  witbin  an  hour  or  more  subsequent 
to  the  testing. 

Marris'  report  records  111  cases  of  typhoid  inffttions  in  which  a  diag- 
nosis was  definitely  established  through  the  isolation  of  the  organism  from 
blood  cultures.  The  atropin  test  was  accurate  in  98  per  cent.  In  these  cases 
the  pulse  acceleration  averaged  only  6.6  beats  per  minute.  In  another  group 
of  patients  observed  by  the  same  writer,  of  247  diagnosed  by  the  less  defi- 
nite agglutination  method  as  having  typhoid,  222  reacted  accurately  to  the 
test.  Agglutination  as  a  diagnosis  procedure  has  become  of  less  value  be- 
cause of  frequent  agglutination  concomitant  to  typhoid  prophylaxis. 


MINJo     1      Z     3    4    5    ■.      7     »     9    10   JSJt  37  3«39-W   ♦<  -"i  -13  «-«3  *  -l?  1»  49  Jo 

'6    _                                                                 \                                  t 

it 

n                                        t                t 

- :                  7       ,  ^ 

«                       \     t^ 

%               '        I 

u 

1 

«                     -  i 

76                                                               i 

«                                        i 

71                                                                                            D 

if 

fL 

u.                                              ^ 

(.4                                                                            / 

tz                                            / 

K 

^g^^^^       __._.._ 

Cliart  2.     Typical  ne 
fcstation  similar  to  thos 


n  test  in  measles  patient  presenting 
;-nt  in  Chart  1. 


At  the  Royal  Victoria  Hospital  in  Montreal,  Mason-  made  use  of  the 
atropin  test  as  a  diagnostic  aid  during  an  epidemic  of  typhoid  infections. 
The  technic  employed  was  essentially  that  described  by  Marris.  In  ail,  265 
tests  were  made  in  sixty-three  cases  of  typhoid  or  paratyphoid.  Fifty-six 
of  the  number  were  cases  of  typhoid  fever  established  by  positive  blood 
cultures  or  liy  W'idal  reactions  in  dilution  higher  than  one  in  forty.  Five 
of  the  cases  were  paratyphoid  B,  diagnosed  bacteriologically,  while  the  re- 
maining two  cases  were  clinically  typhoid  but  the  diagnosis  was  uncon- 
firmed by  any  bacteriologic  or  serologic  findings.  Of  the  total  number 
(sixty-three  patients),  fifty-seven  were  males  and  six  were  females;  no  sex 
variations  were  observed.  Eleven  of  the  sixty-three  failed  to  give  a  posi- 
tive reaction  to  the  atropin  test.     This  departure  from  the  anticipated  posi- 

2.      Mason.    E.    H.:      The    \  alue   of   the   .Mropin    TcM    in    Ihe    Diaenosis   of   Typhoid    Kever,    Arch. 


RANSOHOFF  MEMORIAL  VOLUME 


tive  reaction  is  attril)iited  by  Mason  to  be  due  in  part  to  the  fact  that  in  cer- 
tain cases  only  one  test  was  carried  out,  in  part  to  the  restlessness  of  some 
of  the  patients  under  test  conditions.  The  reaction  became  positive  about 
the  tenth  day  and  disappeared  about  the  thirty-first  day  of  the  infection. 
As  a  check  for  these  known  typhoid  and  paratyphoid  cases,  the  test  was 
applied  to  forty-six  patients  suffering  from  various  clinical  conditions  other 
than  the  typhoids.  Forty-three  yielded  the  anticipated  negative  reaction, 
averaging  in  cardiac  acceleration  21.5  beats  per  minute.    Three  gave  positive 


™ 

0     1   U    3    +   •^    '■M^    ^ 

-'kK4kM+hkhhH+ 

'          ■     '^""■ 

1 

\r^^^ 

102 

L     M 

-^ 

--^;£:.^4--l-UffllllllllM- 

Chart  3.  Typical  positive  atropin  re 
clition  was  the  same  as  that  nf  the  pati< 
five  minutes 


ion  in  pneumonia  patient  whose  clinical  con- 
in  Chart  4.     Broken  line,  interval  of  twenty- 


reactions  without  any  probability  of  enteric  infection.  Mason  concludes 
that  in  the  diagnosis  of  fevers  of  the  typhoid  group,  the  atropin  test  is  of 
distinct  value  and  in  many  cases  afifords  diagnostic  data  prior  to  a  positive 
W'idal  reaction. 


TECHXIC.VL  DAT.V  FROM  THE  PRESEXT  TN\'ESTlG.\TIOX. 
Early  in  our  series  of  tests  it  was  obvious  that  our  results  would  be  at 
variance  to  the  foregoing,  for  which  reason  it  was  deemed  desirable  that  our 
technic  should  conform  in  as  many  respects  as  possible  to  the  previous  work. 
This  necessitated  the  discarding  from  our  .series  the  results  from  fifty-eight 
cases  in  which  technical  innovations  had  been  introduced.  In  the  remain- 
ing 170  cases,  198  tests  have  been  carried  out  with  rigid  adherence  to  the 
Marris  technic.  The  patients  on  whom  these  tests  have  been  made  were  all 
men,  predominantly  of  the  third  decade.  All  had  received  typhoid-para- 
typhoid prophylaxis.  These  men  were  patients  suffering  froin  the  diverse 
conditions  given  in  the  accompanying  table.  In  one  group  of  170  cases, 
108  (63.6  per  cent.)  were  sensiti\e  to  atropin  (atropin  negative  test),  while 
sixty-two  (36.4  per  cent.)  were  nonsensitive  to  atropin.  giving  the  reaction 
described  as  typical  for  typhoid  infections.  Neither  the  positive  nor  the 
negative  atropin  tests  were  sharply  associated  with  any  particular  condi- 
tions. It  may  be  observed  in  the  table  that  in  the  various  listed  processes, 
the  ])ositivc  and  the  negative  are  almost  unitormly  distributed  in  the  ratio.s 
noted  above.  Charts  1  and  2  are  records  of  the  occurrence  of  distinct  posi- 
tive and  negative  atropin  tests,  respectively,  obtained  in  two  measles  cases 
similar  in  clinical  characteristics.  Charts  3  and  4  likewise  were  obtained, 
respectively,  in  two  cases  of  lobar  pneumonia  of  approximately  tlie  same 
degree  of  severity  and  at  about  the  same  stage  of  the  process. 

Page   133 


ALFRED  FRIEDLANDER  AND  CAREY  P.  McCORD 


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s 

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Chart   4.     Typical   negative   atropiii   re 
condition  was  the  same  as  tliat  of  the  patii 


:ion   in   pneumonia   patient   wliose 
in  Chart  3. 


On  two  successive  days  the  atropin  test  was  tnade  on  twenty-seven 
patients  thus  distributed:  influenza.  11;  pleurisy,  3;  pneumonia  (lobar),  2; 
])neumonia  (bronchial),  1;  Ijronchitis.  acute,  4;  tonsillitis,  5;  ethmoidilis,  1. 


RESULTS  OF  TESTS. 


Total 

Number   of 

Cases 


Measles   

Scarlet  fever  

Influenza  

Tonsillitis  

Laryngitis  

Pharyngitis    

Bronchitis    

Pneumonia  

Pleurisy    

Bronchopneumonia   

Mumps    

Mumps-measles    

Meningitis  carrier  

Diphtheria  carrier  

Diphtheria   

Ethmoiditis    

Neuritis  

Adenitis    

Gastric  ulcer  

Intestinal  stasis    

Hyperchlorhydria  

Arthritis,  chronic 

Tuberculosis,  pulmonary 

Jaundice,  catarrhal   

Tapeworm    

Heart  block  

Hyperthryroidism    

Secondary  anemia 

Total 


18 

6 

12 

23 

19 

4 

S 

J 

3 
0 

T 

0 

5 

1 

22 

13 

9 

1 

^j 

9 

0 

2 

0 

6 

3 

4 

I 

0 

1 

0 
0 

0 
0 

1 
1 

1 

0 
0 

1 
1 

0 
0 
0 
0 

1 

0 

RAXSOHOFF  MFMORIAL  VOLUME 


It  was  observed  that  of  the  total  number,  fifteen  patients  were  atropin  sen- 
sitive on  both  days,  four  were  atropin  nonsensitive  on  both  days,  and  eight 
were  within  the  limits  of  atropin  positive  on  one  day  and  atropin  negative 
the  other  day.  The  last  named  group  of  eight  may  not  be  cited  as  evidence 
of  shifting  from  an  atropin  sensitive  to  an  atropin  non-sensitive  state,  for 
the  pulse  rate  changes  were  such  as  to  fall  in  one  day's  test  just  above  or  just 
below  the  arbitrarily  chosen  line  of  demarcation,  and  on  the  following  day 
to  fall  on  the  opposite  side  of  the  line  without  there  having  occurred  an 
actual  pulse  rate  variation  of  more  than  six  or  eight  beats.  Apart  from 
these  borderline  cases,  the  results  obtained  on  the  two  successive  days  were 
closely  alike,  as  shown  in  the  plotted  results  in  one  case  (Chart  5). 

In  none  of  the  sixty-two  cases  giving  rise  to  results  that  under  the  \ivo- 
visions  of  the  test  would  be  interpreted  as  typhoid  infections  were  there 
evidenced  any  clinical  or  laboratory  findings  that  might  remotely  be  attrib- 
uted to  typhoid  or  paratyjihoid  fe\er. 


/«tliy|o   1    z   5  4   5    b    7    8   <>   ,o^Xi^,3^3^i9'u^4  *^^i'^*^s'<^^■,  it  A^  i^ 

pur^E ■■■■■-  "     Y ,, 

'«                    \         s^ ^  ».        ^ 

'" "                  (        ^  t  ^  *^^*- 

'"  ■                           7      s^^^                ^    - 

"^«.2    ^ 

no                                                       ^ 

114                                                                          ' 

I'l                                                                        1 

110                                                                   1 

lOi                                                                       '/ 

""■                                             '  f 

'"*     /jaGrtiTiAtropilSu  >h»»«  5^                  " 

ICZ                                 \                          i"   J_    " 

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^  -    i    ^v'            4 

'^  >                 1                        " : 

Chai 
'  days 


Conformity  of  results  of  two  negative  atropin  reac 
patient  convalescing  from  lobar  pneumonia. 


CO.MMEXT. 
The  conception  of  a  specificity  of  antagonism  of  action  between  atropin 
and  typhotoxins  is  in  no  way  borne  out  by  the  results  of  our  investigation. 
The  occurrence  of  36.4  ])er  cent,  positive  atropin  reactions  in  a  series  of 
170  nontyphoid  cases  removes  from  this  test  all  but  the  most  casual  signifi- 
cance as  a  diagnostic  procedure.  The  factors  that  determine  the  degree  of 
response  of  the  heart  to  atropin  action  are  fundamentally  the  outgrowth  of 
variations  in  the  equilibration  of  the  vegetative  nervous  system.  This  lack 
of  sensitiveness  to  atropin  is  not  peculiar  to  typhoid  infections,  but  is  detect- 


ALFRED  FRIEDLANDER  AND  CAREY  P.  McCORD 

able  in  many  diseases  and,  in   fact,  may  frequently  be  elicited  in  normal 
individuals  as  a  mark  of  vegetative  nervous  system  instability. 

Not  only  in  other  conditions  than  typhoid  is  this  insensitiveness  to  atropin 
encountered ;  but  also  in  typhoid  infections  marked  cardiac  acceleration  may 
))e  observed,  according  to  Matsua  and  Murakami, ■*  who  say :  "In  our  forty- 
six  cases  of  typhoid  fever  (including  seven  cases  of  paratyphoid  B),  atropin 
was  quite  active,  accelerating  the  rate  of  pulse,  especially  in  cases  of  brady- 
cardia. As  all  our  cases  were  serologically  and  bacteriologically  controlled, 
the  diagnosis  was  undoubtedly  correct."  It  is  noteworthy  that  such  typhoid 
])atients  as  exhibited  a  bradycardia  exhibited  cardiac  acceleration  after 
atropin,  while  the  patients  presenting  a  relative  tachycardia  were  for  the 
most  part  unafifected  by  atropin.  In  the  series  cited  by  Matsuo  and  Mura- 
kami, all  the  fatalities  occurred  among  the  number  giving  positive  atropin 
reactions.  This  observation  is  in  keeping  with  the  well  established  fact  that 
a  tachycardia  in  typhoid  bespeaks  a  pessimistic  prognosis.  The  atropin  re- 
action for  this  reason  may  attain  to  definite  prognostic  value. 

SUMMARY. 
A  series  of  170  nontyphoid  patients  has  been  tested  with  the  atropin 
reaction  in  the  manner  described  as  reliable  for  establishing  the  presence  or 
absence  of  typhoid  or  paratyphoid  infections.  Thirty-six  per  cent,  of  the 
number  examined  yielded  results  characteristic  of  typhoid.  Those  cases 
giving  reactions  typical  of  typhoid  without  any  evidence  of  typhoid  existence 
were  distributed  over  thirteen  diseases.  It  is  concluded  from  so  high  a 
percentage  of  discrepancies  that  the  atropin  reaction  is  witliout  esjjecial  value 
in  the  detection  of  typhoid  infection. 


NOTE  ON  THE  INFLUENCE  OF  FOOD  UPON  THE  INTESTINAL 

FLORA  OF  INFANTS.* 

Rv  Alfrrd  Friedlander,  M.D.. 

AND 

J.    \rCT()U    C.KKKNEBAUM,    M.D., 

Cincinnati. 


As  a  preliininaiv  to  the  .studies  about  to  be  reported,  routine  stool  ex- 
aminations were  made  on  fifteen  marantic  infants,  all  under  one  year  of  age, 
in  the  children's  ward  of  the  Cincinnati  Hospital.  The  following  schedule 
was  observed :  The  stool  in  each  case  was  collected  on  sterile  gauze,  marked 
and  placed  in  an  ice  pail  till  examined,  the  time  varying  from  thirty  minutes 
to  twelve  hours. 

Every  stool  was  examined  macroscopically  (size,  shape,  color,  con- 
sistency, abnormalities,  such  as  curds,  mucus  and  blood).  Microscopically, 
fats,  neutral  fats,  fatty  acids,  soaps,  starch,  crystals,  abnormal  constituents 
such  as  cells.' 

A  Gram  smear  was  then  made  and  inoculation  made  into  the  various 
media  to  be  mentioned.  This  technique  was  followed  in  all  cases  except 
that  in  the  study  of  the  two  special  cases  the  stool  was  collected  by  means 
of  a  sterile  anal  tube  after  the  method  of  Kendall. - 

Routine  examination  for  the  bacillus  aerogenes  capsulatus  (B.  Welchii), 
according  to  the  methods  of  Herter^  and  Kendall,*  showed  conclusively  that 
the  gas  bacillus  was  not  a  common  or  a  constant  factor  in  the  cases  studied. 
Forty-six  tests  were  made  in  the  twelve  children,  five  cases  showing  a  posi- 
tive reaction  for  a  total  of  eleven  positive  finds.  The  two  cases  subsequently 
selected  for  special  study  had  seven  of  these  eleven  positive  reactions.  Tests 
for  dysentery,  typhoid  and  paratyphoid  were  negative  in  all  cases. 

The  two  special  cases  showed  practically  the  same  clinical  picture,  and, 
though  of  dififerent  ages,  were  taking  approximately  the  same  kind  and 
amount  of  food.  Their  stools  were  similar,  macroscopically  and  microscopi- 
cally. They  both  presented  typical  marantic  pictures.  In  both  cases  various 
food  modifications,  for  the  most  part  containing  high  percentages  of  maltose, 
cane  sugar  or  lactose,  had  been  tried.  Neither  case  had  done  well  on  these 
mixtures.  It  appeared  to  us  of  interest  to  study  the  intestinal  flora  in  these 
two  cases  in  detail,  attempting  to  ascertain  whether  definite  change  in  the 
bacterial  picture  could  be  brought  about  by  change  of  food. 

This  method  of  studying  the  biology  of  the  intestinal  flora  was  similar  to 
that  adopted  by  Kendall"'  in  his  work  upon  monkeys,  from  which  he  deter- 
mined that  putrefactive  flora  developed  on  a  proteid  diet,  acidophilic  on  a 
carbohydrate  diet.  Accordingly,  these  two  children,  after  a  complete  series 
of  examinations  of  the  iiUestinal  flora  had  been  made,  were  given  Finkel- 


ALFRED  FRIEULANPER  AND  J.  VICTOR  GREEN EBAUM 

stein's  albuminized  milk."  The  formula  of  this  food  is  approximately  fat. 
2  per  cent.;  sugar,  1.5  per  cent.;  proteid,  3  per  cent. 

Each  child  was  given  seven  ounces  every  three  hours — six  feedings  in 
twenty-four  hours.  The  forty-two  ounces  for  each  child  daily  gave  a  caloric 
value  of  498,  and  supplied  6.4  grams  nitrogen.  We  selected  this  food  for 
the  following  reasons: 

(  1  )  The  children  had  both  done  poorly  on  food  with  higher  sugar  con- 
tent. 

(2)  For  the  well-known  therapeutic  effect  of  lactic  acid  bacilli  in  cases 
showing  presence  of  gas  bacillus  (which  both  these  children  had  done). 

(3)  To  obtain  the  high  proteid  in  proportion  to  sugar  content. 

(4)  To  determine  the  effects  clinically,  and  from  the  standpoint  of  in- 
testinal flora  biologically,  upon  cases  for  whom  a  priori  such  food  might  be 
considered  indicated. 

After  the  children  had  been  upon  this  albuminized  milk  for  three  weeks, 
complete  series  of  bacteriologic  tests  were  made  at  intervals  of  a  week, 
using  stools  collected  by  the  anal  tube  for  this  purpose.  Daily  examina- 
tions of  stools  collected  in  the  ordinary  manner  (sterile  gauze,  ice  pail)  were 
also  made.  The  day  after  the  .second  anal  tube  specimen  was  obtained  (the 
children  had  been  on  the  Finkelstein  milk  for  four  weeks)  the  food  was 
again  changed.  The  children  were  now  given  a  mixture  containing  ap- 
])roximately  fat.  2  per  cent. ;  sugar,  7  per  cent. ;  proteid,  3  per  cent,  made 
by  modification  of  certified  milk.*  Each  child  was  given  seven  ounces  of 
this  mixtures  every  three  hours — six  feedings  in  twenty-four  hours.  This 
food  has  a  caloric  value  of  791,  and  a  nitrogen  content  of  6.4  grams. 

This  food  was  selected  because : 

(Ij  The  children,  though  in  better  general  condition  while  on  the 
Finkelstein  diet,  did  not  show  a  sufficient  increase  of  weight.  An  increase 
of  the  caloric  value  of  the  food  was  thus  indicated.  We  chose  to  increase 
the  sugar,  using  lactose,  because  from  our  experience  in  the  Cincinnati 
Hospital  and  the  Boston  Floating  Hospital  we  had  not  found  the  lactose 
as  injurious  as  the  Finkelstein  school  would  make  it  out  to  be.  Besides  the 
children  had  previously  had  other  sugars  without  good  effect. 

( 2 )  To  replace  the  salts  which  the  Finkelstein  food  reduces. 

(3)  Because  examination  now  .showed  absence  of  gas  bacillus,  so  that 
excessive  amounts  of  lactic  acid  bacilli  were  not  needed. 

The  same  observations  and  bacteriologic  tests  upon  specimens  obtained 
with  the  anal  tube  were  made,  after  the  children  had  been  taking  the  food 
for  three  weeks  and  were  repeated  one  week  later.  As  before,  daily  ex- 
aminations of  stools  obtained  in  the  ordinary  way  were  carried  out. 

The  routine  bacteriologic  tests  carried  out  in  both  cases  consisted  of  in- 
oculations of  fermentation  tubes  of  sterile  milk,  broths  with  1  per  cent, 
each  of  saccharose,  dextrose  and  lactose ;  2  per  cent,  dextrose,  with  0.6  per 


RANSOM  OFF  MFMORIAL  VOLUMF 


cent.,  or  "/,„,  acetic  acid,  and  1.2  per  cent.,  or  "/_-,  acid,  aerobic  gelatin 
stabs,  miik  and  litmus  milk  test  tubes,  anaerobic  gelatin  test  tubes  (Wright's 
method),  and  both  gas  bacillus  tests  were  made  daily.  Gram  smears  of  the 
fermentation  tube  sediments  were  made  at  the  end  of  five  days.  The  de- 
tailed bacteriologic  fiindings,  together  with  details  as  to  chemical  and  niicro- 
sco])ic  examinations  of  the  stools,  are  attached  to  this  report. 
The  condensed  report  of  the  two  cases  follows: 

C.'\SE  I. 

Hazel  Reed.  Aged  eight  months  in  November,  1911.  Admitted  to  hos- 
pital August.  1911.  Diagnosis  at  that  time,  gastroenteritis.  Typical  atrophic 
picture. 

PijRion  I.    Entrance  to  November  18,  1911. 

Foods  Used. — Various  modilications  of  milk  and  barley  water,  formulae 
containing  high  percentages  of  maltose,  cane  sugar  and  lactose.  General 
condition  during  this  period  changed  but  little.  On  entrance  weight  was 
seven  and  one-half  pounds.  There  were  occasional  slight  gains,  but  the 
general  trend  was  downward  until  at  the  end  of  the  period  the  weight  was 
six  and  one-half  pounds.  Temperature  practically  normal  throughout  the 
period. 

The  stools  averaged  one  to  two  per  day,  soft  to  pasty  green,  with  occa- 
sional curds  and  mucus.  They  showed  fatty  acid  crystals  in  abundance. 
Gram  fecal  smears :  Gram  negative  always  with  one  exception.  'i\vo  pre- 
sumptive reactions  for  gas  bacillus  out  of  five  tests. 

Period  II.'    November  18.  1911,  to  December  20,  1911. 

Food  Given. —  Albuminized  milk  (Finkelstein).  Slight  but  steady  gain 
in  weight  to  eight  pounds,  a  gain  of  l.i  pounds  in  four  weeks.  The  tem- 
perature remained  normal.  Urine  showed  no  indican.  The  stools  averaged 
one  per  day,  constipated,  grayish-yellow,  no  curds.  Microscopically,  some 
fatty  acids  and  crystals.  Reaction,  alkaline.  Gram  fecal  smear:  Gram 
negative  predominate.  Gram  positive  once. 

Bacteriology. — Stools  collected  in  ordinary  way.  Two  presumptive  gas 
bacillus  tests  two  and  three  days  after  the  food  was  begun,  negative  after 
that.  Considerable  activity  in  milk.  (Stormy  fermentation.)  Gelatin: 
Considerable  liquefaction  and  gas.  Litmus  sugar  and  broth  test  tubes=acid 
and  occasional  gas.  Anal  tube  stools :  Considerable  activity  in  all  media. 
See  summary  in  chart. 

Period  III.    December  20.  1911.  to  January  15,  1912. 

Food. — Certified  milk  modification.  Fat,  2  per  cent.;  sugar,  7  per  cent.; 
proteid,  3  per  cent.  General  condition  strikingly  improved.  Rapid  gain  of 
weight,  one-half  pound  in  first  four  days.  Total  gain  of  2.4  pounds  in 
twenty-six  days.  Temperature  practically  normal  throughout  the  period 
except  for  one  period  of  thirty-six  hours.  The  lower  incisor  teeth  appeared 
at  this  time.  Stools,  one  to  two  daily,  soft  to  pasty  yellow  with  occasionid 
curds  (proteid  by  formalin  test).     Fatty  acids  and  crystals. 

Page  m 


ALFRED  FRIEDLANDER  AND  J.  VICrOR  GREENEBAUM 

Gram  fecal  smears :    Negative  predominate. 

Hactcriolngy. — No  presumptive  gas  bacillus  tests.  Somewhat  less  activ- 
ity in  milk  and  gelatin,  liquefaction  present  but  decreasing. 

Anal  tube  stools:  Somewhat  less  activity  in  media,  liut  same  types  of  re- 
actions were  present.     See  summary  in  chart. 

We  had  thus  definite  and  striking  changes  in  the  general  condition  and 
weight  of  the  child  and  in  the  gross  character  of  the  stools  in  both  tlie 
second  and  third  feeding  periods.  (Albuminized  milk  and  modified  certified 
milk.)  The  improvement  was  much  more  marked  in  the  <hird  than  in  the 
second  period. 

There  was  absence  of  any  striking  change  in  the  Gram  smears  and  bac- 
teriologic  reactions  of  the  intestinal  flora,  merely  a  gradual  decrease  in  gen- 
eral activity  in  the  third  period. 

There  was  absence  of  gas  bacillus  reaction  after  the  third  day  of  Finkel- 
stein  diet.  The  child  continued  to  gain  in  weight  after  the  conclusion  of  the 
third  experimental  period  and  was  discharged  in  excellent  condition. 

CASE  II. 

Lizzie  Clifford,  aged  about  one  year  in  November,  1911.  Admitted  Se])- 
tember,  1911.    Diagnosis,  gastroenteritis.     Typical  atrophic  iiicture. 

PURiOD  I.     August,  1911,  to  November  18,  1911. 

Food. — Milk  and  barley  water  formulas  containing  high  percentages  of 
maltose,  cane  sugar  and  lactose.  Formula,  fat,  3  per  cent. ;  sugar,  3.5  per 
cent. ;  proteid,  2.8  per  cent. 

The  general  condition  showed  no  particular  improvement.  The  weight, 
which  on  entrance  was  10.6  pounds,  showed  slight  gains  and  losses,  but  in 
general  remained  about  the  same.  As  a  rule,  the  temperature  was  normal. 
Stools  one  to  two  daily — yellowish-green  with  frequent  curds  and  mucus. 
Constipation  at  times ;  castor  oil  given  frequently. 

Microscopically,  the  stools  showed  a  moderate  amount  of  fatty  acid 
crystals  and  .soap.  Gram  fecal  smears  were  generally  negative ;  positive 
twice.    One  presumptive  gas  bacillus  reaction  out  of  three  tests. 

Pkrioi)  II.    November  18,  1911,  to  December  20,  1911. 

Food. — Albuminized  milk,  given  in  same  manner  as  in  Case  I.  The 
general  condition  was  distinctly  better.  There  was  an  increase  of  weight  of 
one  pound  in  four  weeks.  Temperature  normal.  Urine  showed  no  indican. 
Stools :    One,  rarely  two  per  day,  pasty  yellow,  no  curds  or  mucus. 

Microscopically,  a  few  fatty  acid  crystals,  some  soap.  The  Gram  fecal 
smears  were  predominantly  negative,  positive  three  times  out  of  ten  ex- 
aminations. 

Bacteriology. — Gas  bacillus  reaction  on  third  and  fourth  days  after  the 
Finkelstein  food  was  begun,  but  negative  thereafter;  stools  obtained  in  ordi- 
nary way  showed  acid  and  some  gas  on  litmus  sugar  and  broth  test  tubes, 
(^n  milk  and  gelatin  there  was  no  particularly  active  reaction.  The  anal 
tube  specimens  showed  marked  activity  on  all  media.     (Summary  on  ciiart.) 

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ALFRED  FRIED  LAN  PER  AND  J.  VICTOR  GREEN  EBAUM 

Period  III.     December  20,  1911,  to  January  15,  1912. 

Food. — Modified  certified  milk,  fat,  2  per  cent. ;  sugar,  7  per  cent. ;  pro- 
leid,  3  per  cent.  General  condition  strikingly  improved.  Child  gained  three 
pounds  in  twenty-six  days.  Temperature  normal,  practically  during  whole 
period.  Stools,  one  to  two  daily.  Pasty,  yellow,  soft,  with  occasional  curds. 
Reaction,  alkaline. 

Microscopically,  alnmdant  fatty  acid  crystals  and  soap.  Gram  fecal 
smears:  Gram  negative  with  increased  numbers  of  Gram  positive  or- 
ganisms ;  Gram  positive  three  times. 

Bacteriology. — No  gas  bacillus  reactions.  Very  little  reaction  in  the 
milk  test  tubes,  very  moderate  reaction  in  gelatin.  Anal  tubes  specimens 
showed  activity  on  all  media,  but  in  general  less  than  that  seen  in  Period  II. 
(Summary  on  chart.) 

The  child  was  discharged  in  excellent  condition.  We  had  in  this  case 
distinct  improvement  in  the  general  condition,  weight  and  gross  character 
of  the  stools  in  both  the  second  and  third  periods,  though  the  changes  were 
much  more  marked  in  the  third  period. 

There  were  no  striking  changes  in  the  bacteriologic  reactions,  though 
there  was  some  decrease  in  activity  in  the  third  period.  The  Gram  fecal 
smears,  however,  took  on  a  decided  positive  appearance  in  the  third  period. 
There  were  no  gas  bacilli  reactions  after  the  third  day  on  Finkelstein's  diet. 

SPECIAL  NOTES  REL-ATING  TO  BACTERIOLOGIC  FINDS  NOT  CHARTl'.D 
ABOVE. 

Milk  Fcnncntation  Tubes. — Same  type  of  reaction  with  both  foods. 

Gram  Smears. — Gram  -|-.  Occasional  branched  forms  (probably  bacillus 
bifidus)  on  both  foods,     Predominace  of  yeasts  on  Finkelstein's  food. 

Milk  Test  Tube. — Distinctly  greater  activity  (coagulation  gas  and  diges- 
tion) in  Period  II.     (On  Finkelstein's  food.) 

Aerobic  Gelatin. — Marked  activity  (complete  liquefaction)  in  first  test, 
but  second  test  in  both  cases  on  Finkelstein's  diet  showing  slighter  reaction 
than  in  either  of  tests  on  2-7-3  food. 

Anaerobic  Gelatin. — Same  as  in  aerobic  gelatin  except  in  general  less 
activity.     No  liquefaction  present  on  second  test  on  Finkelstein's  food. 

FERMENTATION  TUBES. 

Lactose. — All  tubes  showed  cloudiness  and  gas.  Average  gas  production 
in  centimeters  somewhat  more  in  Period  II  (Finkelstein)  than  in  Period  III 
(2-7-3).  Smears  of  sediment  branched  rods  (probably  bacillus  bifidus) 
present  in  both  foods  (greatest  number  on  Finkelstein's  food).  Many 
yeasts  present  in  this  first  test.  (Yeasts  constantly  present  in  fecal  smears 
in  both  cases.) 

Dextrose. — All  tubes  showed  cloudiness  and  gas.  Average  in  centimeters 
greater  on  Finkelstein's  food  than  on  2-7-3.  Most  gas  produced  in  this 
sugar,  although  only  slightly  greater  than  in  lactose.     Branched  organisms 


RAXSOflOFF  MEMORIAL  VOLUME 


(prubabl}-  bacillus  bifidus )  jJreseiU  on  botli  foods,  yeasts  present  on  both 
foods.     (Greatest  frequency  on  this  sugar.) 

Saccharose. — All  tubes  showed  cloudiness  and  gas,  .Slightly  greater 
amount  in  centimeters  on  Finkelstein's.  Least  amount  of  gas  produced  on 
this  sugar.  Branciied  forms  (probably  bacillus  bifidus)  present  in  all  the 
tests.     Yeasts  present  in  considerable  amounts  on  both  diets. 

"/,„  Acetic  Acid:  T2V0  Per  Cent.  Dextrose. — Question  of  cloudiness  on 
both  diets.  Small  number  of  bacteria  in  smear.  About  the  same  types  con- 
stantly present.  \'arious  sized  Gram  positive  rods  and  diplococci  and  Gram 
negative  rods  and  diplobacilli  present.     Yeast  very  rarely  seen. 

"/-,  Acetic  Acid:  Tiuo  Per  Cent.  Dc.vtrosc. — Question  of  cloudiness  on 
2-7-3  diet.  Few  bacteria,  as  a  rule,  seen  in  the  smears.  Occasional  yeast 
l^resent.  Gram  positive  various  sized  rods,  diplococci  and  diplobacilli,  and 
Gram  negative  rods  and  diplobacilli  present.  Branched  and  knobbed  rods 
(Gram  negative)  appeared  in  Period  III  in  Lizzie's  tubes.  Spore-bearing 
rods  present  in  one  test  of  Hazel's  in  Period  III. 

(Trt.s-  Bacillus  Test. — Negative  on  both  foods.     ( B.  Welchii.) 

(The  non-correspondence  of  the  Gram  smears  of  the  .sediments  with 
each  other  and  with  the  fecal  smears  agrees  with  the  findings  of  Hcrter  and 
KrndalF   rin   this  ]ioint.  ) 

GE.\"Er^-\L  CONCLUSIONS. 

(1)  The  foods  used,  albuminized  milk  and  simple  modified  milk  (fat, 
2  per  cent.;  sugar,  7  per  cent.;  proteid,  3  per  cent.)  had  very  little  influence 
on  the  biologic  reactions  of  the  fecal  flora  as  a  whole.  There  was.  however, 
a  slight  lessening  of  the  putrefactive  reactions  on  the  2-7-3  modification. 
The  acidophilic  flora  remained  about  constant  on  both  foods. 

(2)  Finkelstein's  food  is  buttermilk  with  the  salts  and  sugar  reduced 
and  a  high  percentage  of  finely  divided  proteid.  To  a  great  degree  the 
beneficial  effects  of  the  food  depend  upon  its  lactic  acid  content,  and  in 
giving  the  food  we  are  really  using  lactic  acid  therapy.  The  lactic  acid 
bacillus  flora  formed  during  its  administration  was  continued  when  the  food 
was  changed  to  2-7-3,  because  in  the  latter  instance  the  lactic  acid  was 
formed  from  the  sugar.  In  other  words,  with  both  foods  lactic  acid  therapy 
was  given,  so  that  it  is  not  surprising  that  the  bacteriologic  reactions  were 
similar  in  both  instances. 

(3)  In  striking  contrast  to  the  slight  changes  in  the  intestinal  flora 
there  was  a  remarkable  change  in  the  clinical  aspect  of  the  two  cases.  The 
general  condition  improved  greatly,  as  did  the  gross  character  of  the  stools. 
On  the  Finkelstein  food  there  was  moderate  but  steady  gain  in  weight,  while 
on  the  2-7-3  modification  there  was  very  marked  and  rapid  gain  in  weight. 

(4)  The  Finkelstein  food  was  undoubtedly  of  marked  value  in  both 
these  cases.  After  its  administration  the  gas  bacillus  disappeared  in  each 
case.  Again  the  low  sugar  content  of  the  food  undoubtedly  rested  the 
gastrointestinal  tract,  so  that  after  four  weeks  of  its  use  an  increase  of  sugar 
Pauc  r,.: 


ALFRED  FRIED  LAN  PER  AND  J.  VICTOR  GREENEBAUM 

ad  inaxiiiiuni  (7  per  cent,  lactose)  was  not  only  tolerated,  but  utilized  with 
great  benefit  to  the  child. 

(5)  Finkelstein's  food  is  undoubtedly  of  great  value  for  short  periods 
in  suitable  cases,  for  its  effect  upon  the  intestinal  flora  (substitution  of  acido- 
philic for  putrefactive  organisms)  and  also  because  of  its  power  to  rest  the 
gastrointestinal  tract  by  its  low  sugar  content,  especially  for  cases  previously 
overloaded  with  sugars. 

Our  thanks  are  due  to  Dr.  W.  B.  Wherry,  Professor  of  Bacteriology, 
University  of  Cincinnati,  for  his  helpful  suggestions  and  kind  supervision  of 
the  bacteriologic  work. 

REFERENCES. 

1.  Talbot:     .\rchivc5   of  Pediatrics,   Febn.arv,    1911. 

2.  KeiKlall:     Boston   Medical  and   Surgical  Journal.    March   2.    1911. 

3.  Herter:     "liacterial    Infections    of    the    Dipestive    Tract."    1907. 

4.  Kendall    and    Smith:     Boston    .Medical    and    Surgical    Journal.    -March.    1911. 

5.  Kendall:    Journal  of  Biological   Chemistry,    1911,   \ol.  \'I.  p.   -199. 

6.  Leopold:     .'\rchives  of  Pediatrics,  August,   1910. 

7.  Herter  and   Kendall:     Journal   of  Biological   Chemistry.    1908-1909.    \u\.    \ .    p.   2W. 


TUMORS  OF  THE  MEDIASTINUM.* 

By  \V.  D.  Haines,  M.  D., 

Cincinnati. 

The  classification  of  tumors  is  one  of  the  most  changeahic  and  unsatis- 
factory chapters  in  surgical  pathology ;  each  text-book  contains  a  different 
classification  and  each  author,  like  the  housewife  with  her  sewing  machine, 
thinks  he  has  the  best ;  there  is,  however,  an  encouraging  note  in  the  wide 
discrepancies  contained  in  books  published  within  the  quarter  of  a  century 
just  passed,  in  that  with  the  increase  of  our  knowledge  concerning  casual 
factors  in  the  production  of  tumors  there  has  come  a  gradual  diminution  in 
the  number  of  morbid  conditions  formerly  known  as  tumors.  This  better 
comprehension  of  production  of  tumors  has  resulted  in  the  combining  under 
one  head  of  a  number  of  conditions  which  were  formerly  considered  as  inde- 
pendent. Uppermost  in  this  evolution  is  the  recognition  by  investigators 
that  tumors  are  made  up  of  tissues  normally  present  in  the  human  body;  i.  e.. 
the  new  growth  is  but  a  new  arrangement  of  old  structures.  This  does  not 
imply  that  the  new  growth  is  made  up  of  tissues  identical  with  its  immediate 
surroundings,  but  that  the  component  parts  may  be  found  existing  normally 
in  the  body — chondromata  occurring  in  glandular  tissue,  dermoid  cysts  of  the 
ovary  and  numerous  other  examples  will  come  to  mind  wherein  totally  unlike- 
"foreign"  tissue  has  been  found  in  tumors,  but  upon  examination  we  find 
such  foreign  tissue  exists  as  such  elsewhere  in  the  body,  and  we  leave  to  the 
imagination  the  task  of  explaining  the  presence  of  such  tissue  in  an  imusual 
location. 

By  far  the  greater  number  nf  intratlioracic  tumors  are  located  in  the 
mediastinum,  save  aneurism,  nearly  all  of  theni  have  their  origin  in  the 
glandular  tissue  contained  in  this  space.  Neoplasms  of  the  chest  occurring 
outsid  the  mediastinum  usually  involve  these  spaces  in  the  course  of  their 
development.  While  it  is  manifest  that  the  site  of  the  tumor  will  dominate 
the  clinical  manifestations  which  occompany  its  development  and  determine 
the  line  of  treatment  to  be  instituted,  still  more  importance  attaches  to  de- 
termining the  true  nature  of  the  growth  and  the  effect  it  will  probably  produce 
ui)on  the  surrounding  structures.  The  scheme  of  diagnosis,  therefore,  should 
include  careful  consideration  of  the  early  and  more  or  less  obscure  symptom; 
embracing  muscular  pains,  irregular  heart  action,  difficulty  in  breathing  or 
swallowing,  spasmodic  affections  of  the  laryngeal  muscles,  and  pleuritic  irri- 
tation and  cough  with  or  without  effusion. 

T!ie  following  case  illustrates  some  phases  or  mediastinum  tumors. 

The  patient,  a  merchant,  age  57  years,  could  not  recall  having  had  any  serious 
illness  until  within  the  past  six  months,  at  which  time  the  present  trouble  began.  He 
has  had  to  get  up  once  or  twice  each  night  for  the  past  four  or  five  years  to  urinate. 
Six  months  ago  he  weighed  235  pounds,  which  was  about  his  average  weight ;  to-day 

*  Read  Iieforc  tlie  Western  Surgical  Association.  Denver,  December  8,  1914.  "  From  Surger.v, 
Gynecology   and   Obstetrics,    May.    1915. 

Page  JU 


IV.  D.  HAJNliS 


he  weighs  170  pounds.  Four  months  ago  he  began  to  have  a  distressing  cough,  ai- 
tliough  he  could  raise  nothing  from  the  lungs.  He  sometimes  vomited  during  the 
efifort,  and  this  was  followed  by  marked  relief.  Sliortness  of  Ijreath  had  caused  the 
patient  practically  to  abandon  his  business  affairs.  He  liad  taken  much  medicine 
including  iodides,  without  benefit.  On  more  careful  questioning  the  patient  said  he  had 
had  pain  between  the  shoulders  for  a  year  or  more.  This  was  increased  after  eating 
or  on  lying  down,  and  especially  made  worse  by  rapid  walking  or  lifting.  He  could 
not  lie  on  the  left  side. 

Physical  examination  revealed  a  mottled,  brownish  discoloration  of  the  skin,  with 
prominent  veins:  the  left  chest  seemed  to  be  slightly  fuller  than  the  right,  the  supra- 
clavicular glands  on  the  left  side  were  large  and  movable  but  not  tender:  there  was  a 
slight  bulging  at  the  su])rasternal  notch  :  light  pressure  at  this  point  caused  an  intense 
eougliing  seizure,  following  which  the  patient  was  hoarse  until  after  taking  a  sip  of 
water.  There  was  dullness  over  the  left  chest,  which  extended  as  high  as  the  sixth 
interspace  with  the  patient  in  a  sitting  posture.  This  dullness  changed  with  a  change 
in  the  posture  of  the  patient.  Dullness  behind  the  sternum  extended  a  short  distance 
to  the  right  and  was  continuous  with  the  heart  dullness  on  the  left.  The  breath  sounds 
over  this  area  were  absent  and  they  were  indistinct  over  the  rest  of  the  left  chest 
below  the  scapula.  The  heart  action  was  rapid  and  irregular,  but  no  valvular  disturb- 
ance was  detected. 

Protracted  cough  and  ra|iid  Uiss  of  weight  had  caused  my  consultant  to  regard  th,' 
case  as  one  of  tulicrculnsis.  but  the  absence  of  fever  and  the  fact  that  no  rales  were 
present,  although  the  disorder  had  been  going  on  six  months,  made  it  seem  more 
probable  that  some  more  serious  disease  was  causing  the  pain,  which  had  been  per- 
sistent from  the  beginning. 

The  apical  dullness  was  readily  explained  by  the  presence  of  the  enlarged  glands, 
and  the  absence  of  fever  and  local  muscular  spasm  would  rule  out  a  high  Pott's  thus 
narrowing  the  probable  limits  of  diagnosis  to  two  conditions — aneurism  or  tumor. 

The  rapidity  with  which  emaciation  had  taken  place  (he  had  lost  60  pounds  'n 
six  months)  caused  me  to  favor  malignant  growth  in  the  mediastinum  as  the  most 
probable  ex|il.in,ition  of  the  symptoms  and  physical  findings.  Fluid  aspirated  from  the 
left  plniiir.il  ia\iiy  was  clear  and  the  X-ray  showed  a  distinct  shadow  extending  from 
the  ^upra^t.in.il  ncitich  downward  a  distance  of  2><  inches  and  projecting  beyond  the 

The  growth  was  removed  by  suliperiosteal  resection  of  the  inner  end  of  the  left 
I  lavicle  aud  attached  muscles.  It  was  made  up  of  a  number  of  enlarged  lymph-glands 
rather  loosely  held  together.  Little  difficulty  was  encountered  after  exposing  the 
mediastinum,  as  the  mass  was  shelled  out  easily  by  means  of  the  finger  and  scissors. 

There  was  very  little  haemorrhage  at  the  time  of  operation,  and  save  a  troublesome 
leakage  fnmi  a  large  lymph-duct,  proiiably  the  left  jugular,  the  patient  made  a  smooth 
recovery  and  lived  two  years  after  the  operation,  dying  of  some  brain  trouble.  An 
autopsy  was  not  obtained.     The  laboratory  reported  the  growth  as  a  lymph-sarcoma. 

Another  case  may  also  prove  of  interest. 

.\  man  55  years  old  presented  a  history  similar  to  the  foregoing  and  was  in  ex- 
tremis when  admitted  to  the  hospital.  We  attempted  to  remove  the  growth  by  the 
method  outlined  above,  but  owing  to  the  intimate  attachment  of  the  tumor  to  the 
trachea  complete  removal  was  impossible.  The  growth,  which  sprang  from  the  re- 
mains of  the  thymus,  had  permeated  the  entire  thickness  of  the  tracheal  wall  and 
showed  vegetations  on  the  lining  surface.  The  tracheal  rings  had  been  destroyed  bv 
pressure,  permitting  the  walls  to  collapse  to  such  a  degree  as  almost  to  occlude  the 
lumen. 

As  in  the  preceding  case  herein  reported,  the  method  of  attacking  this  growth 
gave  a  very  good  exposure,  and  we  succeeded  in  removing  part  of  the  tumor  before 
it  became  manifest  that  complete  removal  would  necessitate  resecting  a  segment  of 
ihe  trachea.  The  patient  died  within  the  next  12  hours,  and  this  specimen  was  removed 
after  death.     The  growth  is  a  sarcoma. 

For  our  purpose  we  may  arbitrarily  divide  tiiese  growths  into  benign  an(! 
malignant  tumors,  the  former  group  including  aneurism,  gumina,  and  tuber- 
culosis, tlie  later  inchiding  sarcoma  and  carcinoma.  (  Mher  morbid  growths 
nccin-  in  this  region,  Imi  the  above  are  the  inore  fre(|iient  varieties  and  ail 
Mifficienl  for  consideration  in  a  twenty-minute  paper. 

Pogc   l',.j 


RAXSOHOFF  MFMORIAL  VULUMF 


Conclusions  founded  on  observations  of  the  natural  history  of  these 
several  growths  will  best  serve  us  in  their  early  recognition  and  differential 
diagnosis.  Some  of  these  growths  run  a  much  more  ra])id  course  than 
others;  some  present  marked  constitutional  symptoms  and  serious  iinpair- 
ment  of  the  general  health  long  before  symptoms  referable  to  the  chest 
manifest  themselves. 

Recognition,  therefore,  of  the  wide  difference  in  the  general  as])ect  and 
progress  of  intrathoracic  growths,  aside  from  the  special  features  which  in 
no  small  measure  characterize  each  case,  becomes  paramount  in  the  diag- 
nosis, prognosis,  and  management  of  these  growths.  Malignant  growths,  for 
instance,  as  a  rule  grow  much  more  rapidly  than  the  benign  ones,  destroying 
life  in  from  12  to  18  months.  A  notable  exception  to  this  rule  is  found  in 
lymphosarcomata  springing  from  the  posterior  mediastinal  glands  or  remains 
of  the  thymus.  Such  tumors  may  attain  an  enormous  size  and  the  patient 
live  a  long  time,  death  finally  resulting  in  consequence  of  metastases. 

Growths  springing  from  the  connective  tissue  in  the  mediastinum — 
sarcomata — may  attain  considerable  size  without  producing  symptoms,  this 
being  due  to  the  laxity  of  the  tissue  and  the  ease  with  which  enlargement 
may  take  place  in  all  directions.  To  the  writer's  mind  this  is  a  valuable 
point  to  remember  in  attetnpts  at  localization  of  chest  tumors.  The  site  of 
the  aneurism  is  more  or  less  fixed,  and  you  will  recall  that  it  is  in  this  type  of 
case  that  we  encounter  those  enormous  deformities  of  the  chest,  including 
bulging,  erosion,  and  fracture  of  the  bony  cage.  Extensive  deformity  oc- 
curring relatively  early  in  the  history  of  intrathoracic  neoplasms  may  be 
induced  by  implication  of  a  bronchus,  which  causes  collapse  of  the  corre- 
sponding lung  and  compensatory  expansion  of  the  opposite  side.  Derange- 
ments of  the  circulation  are  constant  concomitants  of  mediastinal  tumors : 
they  are  caused,  not  alone  by  external  pressure  upon  the  vessel  walls,  but 
also  by  the  inherent  tendency  of  sarcomata  to  permeate  the  walls  of  the 
veins,  thereby  inducing  partial  or  complete  occlusion  and  metastases.  The 
effects  are  manifold,  finding  expression  in  oedema,  metastases,  hsemorrhagic 
effusions  into  the  pleura,  pulmonary  and  cerebral  apoplexy,  gangrene,  and 
death. 

Although  functional  disorders  of  the  heart  with  modified  rhythm  and 
sounds,  without  discernible  valvular  or  muscular  impairment,  are  the  usual 
findings,  cases  are  recorded  in  the  literature  wherein  the  heart  has  been  in- 
volved in  a  similar  manner  to  those  rare  cases  of  malignant  breast  in  which 
the  disease,  by  extending  through  the  thoracic  wall,  affected  the  heart.  Pain 
in  some  degree  is  usually  present,  but  the  chief  complaint  of  th  patient  suf- 
fering of  mediastinal  tumor  will  be  of  his  inability  to  get  his  breath;  the 
pain,  cough,  and  aphonia  are  annoying,  but  the  dyspnoea  is  persistent  and 
terrifying,  filling  the  patient's  mind  with  ominous  forebodings,  'i'his,  the 
most  prominent  of  the  subjective  symptoms,  is  characterized  by  a  wide  dis- 
crepancy between  the  amount  of  exercise  and  the  respiratory  disturbance ; 

Pane    I'fi 


ff".  D.  HAIXES 


for  instance,  the  writer  has  seen  a  patient,  the  subject  of  a  mediastinal 
growth,  who  had  been  sitting  in  perfect  comfort,  bring  on  by  merely  walking 
across  the  room  a  violent  spasmodic  coughing  seizure  and  serious  resiiirator;; 
embarrassment. 

From  what  has  been  said  il  becomes  apparent  that  no  one  sigti  or  symp- 
tom or  hitherto  described  order  of  phenomena  can  be  said  to  be  [lathognc- 
monic  of  a  certain  intrathoracic  growth.  The  cases  vary  widely,  but  by 
eliminating  the  ordinary  forms  of  disea.se  in  a  patient  suffering  of  serious 
derangement  of  the  mechanics  of  the  chest,  one  is  warranted  in  making  a 
presumptive  diagnosis  of  mediastinal  tumor. 

In  the  differential  diagnosis  aneurism  stands  out  preeminently  for  first 
consideration.  The  physical  signs  of  aneurism  comprise  a  loud  murmur  or 
splashing  sound,  accompanied  by  a  purring  thrill,  which  is  imparted  to  the 
hand  of  the  examiner  when  placed  on  the  chest,  and  interference  with  arterin/ 
circulation,  delay,  feebleness,  or  absence  of  the  radial,  brachial,  or  carotid 
pulse.  Interference  with  the  return  flow  is  common  to  both  aneurism  and 
solid  tumors,  occurring  nnicli  earlier  in  the  history  of  the  latter  than  in  the 
former. 

Retardation  of  the  radical  ])ulse  on  one  side  may  be  observed  in  cases 
where  an  aneurism  is  situated  distal  to  the  origin  of  the  great  vessels  given 
off  l)y  the  aorta.  Sphygmographic  tracings  are  of  signal  value  in  the  dif- 
ferential, and  comparative  tracings  should  greatly  aid  one  in  definitely  fixing 
the  site  of  the  aneurism. 

Symptoms  dependent  upon  jjressure  manifest  themselves  later  in  aneurism 
than  in  other  growths,  but,  aside  from  this,  possess  no  particular  difference 
which  would  serve  as  aids  in  the  diagnosis.  The  physical  signs  of  aneurism, 
like  those  of  other  intrathoracic  growths,  will  vary  with  the  time  of  observa- 
tion;  if  the  subject  of  an  aneurism  presents  himself  at  a  time  when  there  is 
a  considerable  degree  of  elasticity  in  the  sac-wall  and,  above  all,  at  a  time 
when  fluid  contents  fill  the  sac.  the  classical  expansible  tumor,  peculiar  vibra- 
tory thrill,  and  loud  tumultuous  sounds  render  diagnosis  easy  ;  cjuite  different, 
however,  are  the  signs  after  layer  upon  layer  of  clots  are  deposited  upon 
the  inner  surface  of  the  sac.  Instead  of  a  resilient  sac  we  now  have  to  deal 
with  a  thick,  rigid  wall  which  limits  the  production  of  sounds,  interferes 
with  their  transmission  to  the  ear  of  the  examiner,  and  presents  the  char- 
acteristics of  a  solid  tumor. 

Although  sarcoma  is  the  prevailing  type  of  malignant  tumor  found  in  the 
mediastinum,  carcinomata  are  found  sufficiently  often  to  enable  us  to  sum- 
marize their  leading  clinical  features.  Primary  carcinoma  in  this  region 
has,  in  the  writer's  experience,  more  frequently  begun  in  the  gullet  than  else- 
where, and  the  symptoms  are  those  of  a  slowly  but  steadily  increasing  difli- 
cnlty  in  swallowing;  solids  are  first  discarded  and  in  the  course  of  a  few 
months  the  patient  rapidly  succumbs  if  not  relieved  by  surgical  measures. 


R.IXSOIIOFF  MliMORIAL  VOLUME 


Sarcomata  in  their  early  history  are  painless  and  increase  in  size  slowly 
Owing  to  these  facts  the  patient  does  not  present  himself  until  pressure 
symptoms — cough,  hoarseness,  or  dyspno?a — drive  him  to  seek  council. 

Rapidly  growing  tumors,  like  gummata,  are  painful  very  early  in  their 
course,  and  pressure  symptoms,  irregular  pupil,  aphonia,  and  dilated  sur- 
face veins  and  serious  right  heart  embarrassment  soon  follow.  Growths  i.; 
the  anterior  and  superior  mediastinum  are  in  a  measure  distinguished  by 
pressure  exerted  by  them  upon  the  superior  cava  and  innominate,  while  in- 
terference with  the  inferior  cava  or  azygos  would  suggest  the  presence  of 
a  tumor  in  the  posterior  mediastinum.  Implication  of  the  venous  circulation, 
ciliomotor  roots  of  the  sympathetic,  recurrent  laryngeal  or  pneumogastric, 
relatively  early  in  the  history,  speak  for  solid  tumor  as  contrasted  with 
aneurism,  which  always  shows  symptoms  on  the  part  of  the  arterial  circula- 
tion long  before  venous  stasis  becomes  manifest. 

Tuberculous  adenitis,  leading  to  caseation  and  abscess,  afifect  this  region, 
and  the  enlarged  glands  must  be  differentiated  from  other  growths.  This 
condition,  like  gumma,  is  ordinarily  not  difficult  of  recognition,  as  in  either 
instance  we  are  dealing  with  the  local  expression  of  a  disease  which  has 
almost  innumerable  general  symptoms,  a  sufficient  number  of  which  are 
usually  present  preceding  the  central  chest  lesion  to  readily  distinguish  them 
from  other  conditions  found  in  the  mediastinum,  h'inally,  we  possess  val- 
uable therapeutic  tests  which  will  aid  in  the  differential  diagnosis  of  both 
tuberculous  and  luetic  growths. 

Patients  dead  of  sarcoma  of  the  mediastinum  are  singularl\  free  from 
metastases.  Aloney,  an  English  pathologist,  posted  a  ntnuher  of  bodies  in 
which  the  disease  was  wholly  confined  to  the  mediastinum,  and  the  writer's 
experience  in  the  dead  room  tends  to  con.firm  this  view.  If  Ibis  observation 
proves  true  in  any  considerable  proportion  of  the  cases  of  sarcoma  originat- 
ing in  the  mediastinum,  it  should  encourage  surgeons  in  their  efforts  to  re- 
lieve, by  operation,  a  condition  which  has  hitherto  been  regarded  as  well- 
nigh  hopeless. 

Numerous  methods  have  been  devised  for  exposing  the  anterior  and 
superior  mediastial  sjiaces ;  they  include  trephining,  osteoplastic  flap,  and 
longitudinal  division  of  the  stenuuu ;  these  and  other  operative  procedures 
were  divised  with  a  view  to  dealing  with  aneurisms. 

liardenheuer  separated  the  muscles  subperiosteally  from  the  clavicles  and 
manubrium,  and  then  by  dividing  the  clavicle  and  first  rib  on  one  side  he  wa.; 
able  to  remove  a  growth  from  the  mediastinum.  The  writer  has  employed 
this  method  in  two  instances,  and  while  a  fair  exposure  of  the  field  is  ob- 
tained, there  are  certain  obstacles  which  should  be  regarded  before  attempt- 
ing the  operation.  The  chief  objection  lies  in  the  liability  of  injury  to  the 
l)leura.  Damage  done  to  the  circulation  in  the  course  of  the  o[)eration  ren- 
ders the  field  more  suscei)lilile  lo  infection,  and  lastly  the  o|)rraliiin  i^  tech- 
nically difficult. 

Page   /.(S 


IV.  I).  HAIXIIS 


The  operation  devised  by  Milton  for  ejiposing  the  mediastinum  is  less 
complicated  and  free  from  these  objections,  and  it  gives  a  more  satisfactory 
exposure  of  the  field  for  operation.  He  divided  the  sternum  longitudinally 
throughout  its  entire  length  in  order  to  remove  a  foreign  body  from  ih;' 
riglit  bronchus,  which  he  successfully  accomplished. 

.American  surgeons,  notably  Curtis,  with  a  view  to  avoiding  injury  fo 
the  pleura  have  modified  the  operation  by  limiting  the  division  to  the 
manubrium,  at  which  poiiU  the  pleura  is  widely  separated. 

As  modified  the  procedure  consists  of  an  incision  which  is  carried  from 
the  larynx  downward  in  the  midline  to  a  point  opposite  the  third  interspace 
The  sternohyoid  and  the  sternomastoi  muscles  are  detached  subperiosteally 
and  are  well  retracted  while  the  manubrium  is  being  divided  longitudinally. 
In  sawing  through  the  bone  the  saw  should  discontinue  on  reaching  th.e 
periosteum  covering  the  posterior  surface  and  a  chisel  should  be  inserted  to 
pry  the  severed  margins  apart.  This  enables  one  to  divide  the  periosteum 
safely  under  the  guidance  of  the  eye. 

Mayo's  blunt  pointed  scissors  are  well  adapted  for  dividing  the  jjeri- 
osteum.  The  margins  of  the  divided  bone  may  be  retracted  two  or  two  and 
one-half  inches,  permitting  the  free  introduction  of  instruments  and  fingers. 
In  doing  the  operation  the  chief  structures  to  be  avoided  are  the  pleura  and 
the  internal  mammary  or  its  branches.  Division  of  the  latter  will  cause 
haemorrhage,  which  is  difficult  to  control. 

The  writer's  experience  with  the  Milton  operation  has  been  limited  to  the 
cadaver.  However,  the  exposure  obtained  Ijy  this  method  will  permit  one 
to  ligale  the  innominate,  carotid,  or  subclavian  and  deal  with  operable  neo- 
plasms in  this  region. 

RKl'l'.RKNCES 
I>.%CuSTA.    Pliysical   lliagnosis.  fl.lNT.     Practice   of   Medicine.  Cahoi.      Uifferenlial    Hiagnosis. 


A  STRIKING  ELE\'ATir)>;  OF  THE  TEMPERATURE  OF  THE 
HAND  AND  FOREARM  FOLLOWING  THE  EXCISION  OF  A 
SUBCLAMAN  ANEURISM  AND  LIGATIONS  OF  THE  LEFT 
SIT.CLAMAN  AND  AXILLARY  ARTERIES.* 

By  \\'IT.I.IAM    S.    HaLSTED 

In  a  series  of  signally  interesting  papers  Professor  Rene  Leriche  calls 
attention  to  the  value  of  what  he  terms  periarterial  sympathectomv  in  the 
treatment  of  various  neuralgias,  local  ischemias,  reflex  contractures  of  the 
Babinski-Froment  type,  and  other  afifections.  Fostered  in  the  traditions  of 
the  schools  of  IMagendie,  Claude  Bernard,  and  Brown  Sequard,  it  wa.s  in 
the  happy  order  of  things  that  it  should  fall  to  the  lot  of  a  surgeon  of  Lyon 
to  turn  to  therapeutic  account  a  discovery  of  the  greatest  of  the  founders  of 
experimental  medicine.  A  devoted  disciple  of  Jaboulay,  Leriche  credits  this 
talented  surgeon,  his  "master,"  with  the  suggestion  which  led  to  the  novel 
and  important  researches  made  by  him  during  the  years  of  the  war. 

My  interest  in  Leriche's  work  has  been  reawakened  by  an  observation 
made  only  a  few  weeks  ago  in  the  Surgical  Clinic  of  The  Johns  Hopkins 
University.  In  1918  I  ligated  the  left  subclavian  and  carotid  arteries  near 
their  origin  from  the  aorta  for  the  cure  of  a  huge  subclavian  aneurism  (Figs. 
1  and  2).  For  a  year  the  aneurism  decreased  steadily  in  size  (Figs.  3,  4, 
5  and  6).  Then  for  a  year  we  lost  track  of  the  patient.  About  two  months 
ago  we  succeeded  in  tracing  him,  and  persuaded  him  to  let  us  excise  the 
aneurism,  which  in  the  period  of  non-observation  had  developed  a  faint 
pulsation  and  become  slightly  larger  (Fig.  7).  About  four  hours  after  this 
operation,  at  which  the  aneurism  was  excised  and  the  subclavian  and  axillary 
arteries  ligated,  it  was  noticed  that  the  left  hand  and  forearm,  which  for  two 
years  had  been  strikingly  cold,  had  become  abnormally  warm — appreciably 
warmer  than  the  corresponding  limb.  Unfortunately,  our  surface  thermom- 
eter had  been  broken  and  we  were  unable  to  obtain  another.  About  five 
weeks  after  the  operation  the  hand  and  forearm  became  cold  again — at  first 
in  small  areas — remaining  cold  for  only  a  day  or  two. 

To-day  (June  28)  the  69th  since  the  operation,  the  back  of  the  left  hand 
is  quite  cold,  whereas  the  left  palm  is  about  as  warm  as  the  right.  The 
temperature  of  the  hand  and  forearm  has  varied  from  day  to  day  and  from 
hour  to  hour;  certain  small,  quite  well-defined  areas  have  remained  uni- 
formly cool;  otherwise,  the  hand  and  forearm  have  maintained  their  normal 
warmth. 

SuR.  No.  46179.  .Mexander  Miller.  Xegro,  ,-et  29.  .-Xtlmittcd  to  The  lohns  Hopkins 
Hospital  .Npril  22,   1918;  discharged  .August  12,  1918. 

The  patient  states  that  he  has  always  been  perfectly  well.  In  April,  1917,  he 
noticed  a  swelling  about  the  size  of  an  egg  above  the  left  clavicle.  .Mmost  simultane- 
ously with  the  recognition  of  the  swelling,  pain  and  numbness  in  the  upper  extremity 
were  observel.  The  growth  of  the  tumor  was  gradual  until  about  .March,  1918;  since 
then  it  has  been  very  rapid.  For  the  past  two  weeks  the  liml)  has  l)een  totally  par- 
alyzed. The  patient  recalls  that  until  Christmas,  1917,  lie  could  still  raise  his  arm  a 
little. 

•  From  The  Jr.hn«  Hopkins  Hospital    Hiillelii.,  July,    I'J2o'. 


WILLIAM  S.  HALSTED 


The  J, •hut  Hophiiis  Hospital  Bulletin.  July.  IQ.'O 


Fig    1  — Aneurism  of  the  left  sub- 
clavian artei-\, 
Alexander   Miller.   April   '22,   1918. 


Alexander   xMiller,   Aim!   22,    11)18. 


Fig.    3.— Alexander    Miller,    109   days 

after  li,c:ation  of  the  subclavian  artery 

nuear  its  origin. 


Fu,.    4.— Alexander   Miller,    109    days 
after  the  ligation. 


RAXSOHOFf  MEMORIAL  rOLL'MH 


The  Johns  Hopkins  Hosfilal  Bulletin,  July,  igjo 


Fu.    .") — Alexander  Miller,  10  months  Fi 

after  the  ligation. 


Alexander  Miller,   In  months 
after  the   ligation. 


Fig.    7.— Alexander    Miller,    2    year.'; 

after   the  ligation  of  the   subclavian, 

and   2   weeks  before   the   excision  of 

tlie  aneurism. 


Fic.    8.— Alexander    Miller.    1    month 
after  excision  of  tlie  aneurism. 


WILLIAM  S.  HALSTED 


About  four  years  liefore  admission  the  patient  was  shot  just  above  the  left 
clavicle.  The  wound  healed  promptly.  The  bullet  was  not  removed  and  has  given  him 
no  indication  of  its  presence. 

Examination. — The  patient  is  evidently  suffering  severe  pain,  and  constantly  sup- 
ports his  left  wrist  with  his  right  hand.  The  pain,  he  says,  is  most  intense  from  the 
clliow-jtjint  to  the  hand  and  in  the  left  shoulder. 

.\  lui^e  aneurism  occupies  the  left  neck  from  the  clavicle  to  the  ear  (Figs.  1  and  2). 
The  head  is  deflected  and  rotated  to  the  right.  The  vertex  of  the  pulsating  mass  is 
about  on  a  plumb-line  dropped  to  the  junction  of  the  middle  and  inner  thirds  of  the 
clavicle.  The  swelling  and  pulsation  extend  on  to  the  chest,  and  the  whole  body  is 
jarred  with  each  heartbeat.  Posteriorly  the  diffuse  pulsating  tumefaction  spreads  out 
to  a  point  below  the  spine  of  the  scapula.  The  aneurism  extends  upward  in  domeshape.' 
a  hand  can  be  inserted  between  it  and  the  face  down  to  the  angle  of  the  lower  jaw. 
The  whole  shoulder  girdle  appears  to  be  raised  away  from  the  chest  wall,  the  acromio- 
clavicular articulation  being  apparently  disrupted.  The  skin  over  the  tumor  is  very 
tense  and  glistening.  From  the  clavicle  to  about  the  level  of  the  nipple  the  brawn.' 
tissues  are  proliably  infiltrated  with  blood  as  well  as  inflammatory  products.  The 
trachea  is  displaced  to  the  right.  A  systolic  bruit,  most  distinct  above  the  inner  third 
of  the  clavicle,  can  be  heard  over  the  greater  part  of  the  pulsating  mass.  Xo  thrill  can 
be  left.  The  left  radial  pulse  is  absent.  There  is  slight  ptosis  of  the  left  eyelid,  but  the 
pupils  respond  equally.  Only  the  inner  third  and  the  acrominal  tip  of  the  clavicle  can 
he  defined  with  the  fingers.  The  remainder  of  the  bone  is  buried  in  the  tumefaction. 
A  bullet  is  palpable  just  beneath  the  skin  to  the  left  and  below  the  spine  of  the  seventh 
cervical  vertebra.  The  left  arm  is  paralyzed.  The  extent  of  the  loss  of  motion  and 
sensation  and  the  degree  of  restoration  of  function  will  be  outlined  in  a  subsequem 
paper. 

Fluroscopk  Examination. — The  shadow  of  the  aneurism  extends  to  the  lower 
border  of  the  clavicle  but  not  to  the  first  rib.  The  heart  seems  not  to  be  enlarged. 
Tlic  right  subclavian  and  carotid  arteries,  distinctly  seen,  are  normal  in  size. 

Skiaijraphic  Report. — Large  mass  in'  left  neck.  Clavicle  deeply  eroded,  perhaps 
fra.gmented.     Bullet  in  upper  dorsal  region. 

(^/■I'Mi/io;;.— April  26,  1918.  Dr.  Halsted.  Ligation  of  the  left  common  carotid  and 
llic  left  snbclavin  arteries  near  their  origin  from  the  aorta. 

Kther.  Wide  protection  of  the  operative  field  with  celloidin-silk.i  Transverse 
bow-incision  just  below  the  cervico-thoracic  junction,  supplemented  by  a  vertical  on'.> 
along  the  left  border  of  the  sternum  (bow  and  plummet  incision).  Free  exposure  of 
manubrium  and  left  sterno-clavicular  joint.  The  incised  tissues  were  oedematous, 
particularly  so  below  the  clavicle.  The  superficial  vessels  were  abnormally  large. 
Careful  hemostasis  by  the  fine  silk  transfixion  method.  The  left  two-thirds  of  the 
manubrium  and  the  left  sterno-clavicular  joint  were  resected  with  the  giant  rongeur 
forceps  of  Esmarch,  care  being  taken  to  avoid  disturbing  the  fragments  of  the  erodeil 
clavicle.  The  thymus  gland  and  the  left  innominate  vein  were  drawn  upward  and  ro 
the  right  with  a  retractor. 

The  trachea  in  the  thorax  as  well  as  in  the  neck  was  displaced  to  the  right  by  thf 
pressure  of  the  aneurism.  The  left  carotid,  deeply  situated  and  occupying  the  midline 
in  the  dust,  was  gently  occluded  with  a  tape  ligature.  This  artery  was  thought  a! 
first  I"  \>r  till-  lift  subclavin  inasmuch  as,  according  to  the  erroneous  testimony  of  an 
ussisiant,  its  .julusidn  did  not  affect  the  pulse  in  the  left  temporal  artery,  and  lessened 
ihe  fiir(c  of  tile  pulsation  in  the  aneurism.  To  obtain  access  to  the  left  subclavin 
artery  the  cartilage  of  the  left  first  rib  and  the  adjoining  margain  of  the  sternum  were 
cut  away.  The  arch,  the  anrtic  isilinius  ,ind  descending  oarta,  and  the  left  auricle  of  the 
heart  were  palpated  with  the  Imutr  "i  the  opeartor  before  the  left  subclavian,  lying 
close  to  the  vertebral  column,  was  identified.  With  the  aid  of  four  long,  narrow 
dissectors,  two  of  which  were  manipulated  by  the  operator  and  two  by  Dr.  Mont 
Reid,  the  vessel  was  clearly  exposed  at  its  origin  from  the  aorta  and  for  several 
centimeters  distal  to  this  point.  As  it  was  evident  that  none  of  the  various  aneurism 
needles  was  suitable  for  the  passage  of  a  ligature  at  this  depth,  a  long,  narrow,  bluiU 
dissector,  slightly  curved  and  pierced  at  its  tip,  was  armed  with  fine  silk  and  passed 
under  the  artery.  By  means  of  this  thread  and  then  another,  linen  tapes  were  drawn 
under  the  subclavin;  both  of  these  were  tied,  the  second  distal  and  close  to  the  firs;, 
with  force  only  sufficient  to  close  completely  the  artery's  lumen.  The  aneurism  be- 
came very  tense  and  hard  immediately  after  the  ligation,  but  was  pulseless. 

The  patient's  condition,  bad  on  admission  and  particularly  so  just  before  operation, 
caused  us  some  anxiety.  Traction  within  the  thorax  on  the  branches  of  the  aortic 
arch  or  on  the  pulmonary  artery  affects  unfavorably  and  eventually  disastrously  the 

IW.    S.    Halsted.      Clinical    and    Experimental    Contributions    to    the    Surgery    of    the    Thorax. 


RAXSOHOFF  MFMORIAL  J-QLUME 


action  of  the  heart.  The  pulse,  about  120  at  the  beginning,  was  140+  and  quite  weaK 
at  the  termination  of  the  operation.  The  wound  was  completely  and  accurately  closed 
with  interrupted  sutures  of  tine  silk.  A  large  dead  space  in  the  mediastinum  was,  natu- 
rally, unavoidable. 

Healing  per  primam. 

November  9,  1918.  The  patient  has  been  examined  frequently  since  his  discharge 
from  the  hospital.  There  has  been  no  pulsation  in  the  aneurism  since  the  operation. 
The  mass  has  steadily  but  slowly  decreased  in  size.  The  patient  can  make  slight  move- 
ments with  the  left  fingers,  otherwise  there  has  l)eLn  no  appreciable  return  of  power 
or  sensation  in  the  paralyzed  arm. 

The  patient  was  observed  frequent])-  throughout  the  year  following  the 
operation.  Slowly  but  steadily  the  inilseless  tumor,  during  this  period, 
diminished  in  size.  Tlien  for  a  year  the  patient.  Hving  out  of  town,  was 
lost  sight  of.  Exactly  two  years  after  the  first  operation  he  returned,  at  our 
solicitation,  to  the  hospital.  Now  for  the  first  time  since  the  operation  a  very 
faint  pulsation  was  discernible.  The  tumor  (Fig.  7)  measured  in  its  trans- 
verse (  frontal )  diameter  precisely  the  same  as  when  last  seen  a  year  before ; 
the  anteroposterior  measurement  (sagittal),  however,  gave  an  increase  of 
about  4  cm.  I  decided  that  the  aneurism  should  be  excised,  and  on  the  20th 
of  April,  1920,  performed  the  operation  as  follows : 

The  skin  over  the  tumor  and  a  wide  area  about  it  were  protected  with  Chme^e 
silk  dipped  in  coUoidin.  The  incision,  made  through  the  tightly  adherent  silk,  ran  with 
the  clavicle  in  its  central  part,  curving  up  into  the  neck  at  its  inner  end,  and  down  alon.i? 
the  cephalic  vein  at  its  outer.  Superimposed  on  and  not  attached  to  the  greatly 
broadened  and  thickened  clavicle  was  a  sharply  convex  bow  of  bone  about  9  cm.  long 
and  6  mm.  thick.  This  bow,  recognizable  in  the  photograph  (Fig.  5),  was  cut  awav 
and  the  clavicle  bitten  through  with  a  heavy  rongeur  forceps  at  two  points  as  close 
to  the  aneurism  as  possible.  The  cephalic  \ein  was  divided,  and  the  axillary  artery — 
pulseless,  reduced  in  size,  but  not  empty — was  ligated  about  at  the  junction  of  its  first 
and  second  portions,  through  a  split  made  in  the  pectoralis  minor  muscle ;  the  third 
portion  of  the  subclavian  artery  was  ligated  above  the  clavicle ;  the  aneurismal  sac, 
and  the  resected  rib  were  excised  in  one  piece.  The  aneurism  was  matted  almo.it 
everywhere  to  the  surrounding  parts  by  dense  connective  tissue,  and  hence  had  to  be 
carved  out  rather  than  enucleated.  The  identification  and  freeing  of  the  roots  of  the 
brachial  plexus,  which  were  in  places  embedded  in  the  wall  of  the  sac,  consumed  much 
time.  The  operation  was  conducted  in  a  bloodless  manner  until  nothing  remained  to  be 
done  except  to  divide  the  narrow  neck  of  the  sac.  The  tissues  of  this  neck  proved  to  be 
thin  and  friable,  and  the  patient  lost  a  few  cubic  centimeters  of  blood  through  the 
slit  in  the  artery — the  mouth  of  the  false  sac — which  was  readily  closed  with  three 
stitches  of  fine  silk.  The  wound  was  closed  without  drainage.  I  am  greatly  indebted 
to  Dr.  Heuer  and  Dr.  Reid  for  their  skilful  and  highly  competent  assistance  which 
enabled  me  without  concern  to  conduct  the  operation  to  a  satisfactory  conclusion. 

At  the  first  dressing,  made  on  the  10th  day  after  operation,  it  was  noted  that  a 
little  fluid  had  accumulated  in  the  outer  part  of  the  wound.  This  was  evacuated 
by  puncture  with  a  wooden  toothpick  wrapped  with  a  few  fibres  of  cotton  dipped  in 
pure  carbolic  acid.  Closure  of  the  puncture  was  prevented  by  the  reapplication  of  the 
acid  in  the  same  manner  on  two  alternate  days.  The  introduction  of  a  drain  of  any 
kind  wc  scrupulously  avoid.  The  word  "drainage  tube"  is  in  disfavor  in  our  clinic. 
Shniild  a  UMunil  become  infected,  tubes  would  be  properly  introduced  for  the  purpose 
of  disinfection,  but  not  for  drainage. 

Noteworthy  is  the  fact  that  the  patient's  hand  and  forearm,  which  prior 
to  and  ever  since  the  first  operation  had  been  markedly  cold,  became  strik- 
ingly warm  about  four  hours  after  the  second  operation  and  have  remained 
warm,  except  in  certain  areas,  to  the  [jresent  time  (June  IS).  It  is  improb- 
able that  the  ligation  of  the  cephalic  vein  was  in  any  part  responsible  for  this 
indubitable  imi^rovement  in  the  circulation.  The  elevation  of  the  tempera- 
ture of  the  liand  and  forearm  must.  I  believe.  l)e  attributable  to  vasodilatation 


WILLIAM  S.  HALSTED 


incident  to  the  ligations  of  the  subclavin  and  axillary  arteries — to  the  crush- 
ing of  their  nerves.  This  question  will  be  discussed  in  the  course  of  the  con- 
sideration of  the  treatment  of  subclavin  aneurisms  in  a  paper  about  to 
appear  in  The  Johns  Hopkins  Hospital  Reports. 

1  have  found  pleasure  in  translating  one  of  the  papers  of  Monsieur 
Leriche,  believing  that  his  work  on  periarterial  sympathectomy  will  at  this 
moment  particularly  interest  surgeons  who  may  have  the  opportunities  and 
the  inclination  to  verify  his  observations.  While  disclaiming  unqualified 
acceptance  of  some  of  his  explanations  and  deductions  which  are  at  variance 
with  the  teachings  of  physiologists  we  must  recognize  that  Leriche's  contribu- 
tions are  of  unusual  interest  and  value  ;  they  will  stimulate  investigation. 

TEUIAKTERIAL  SV.MP.ATHECTO.M V  AND  ITS  RESULTS 
Rene  Leriche 

In  January,  1916,  and  in  April  of  the  same  year,2  I  made  known  the  first  resuh^ 
which  the  denudation  and  e.xcision  of  the  sympathetic  plexuses  around  the  arteries  in 
causalgia  and  in  certain  trophic  troubles  had  given  me.  Since  then  this  operation  has 
been  tried  in  various  ways.  Le  I'Virt,  Cotte,  Sencert,  Lavenant,  de  Massaiy  ami  V'eau, 
Prat,  have  reported  experiences  with  it.  1  personally  ha\c  perf.nin.il  it  ,i7  times' 
The  moment  seems  to  have  come  to  imlicate  briefly  the  essential  facts  wliuh  th,  piocc- 
dure  has  taught  me.  Ivlaborating  the  idea  of  Jaboulay,  we  must  indeed  de\el<ip  a  true 
and  general  i)|i(i-ali\e   method  susceptible  of   very   varied  applications. 

I  think  at  the  otuset  that  it  ought  to  be  designated  liy  an  exact  name:  it  is  a 
peripheral  sympatlieclnm\  which,  according  to  the  lc\'el  wdiere  it  is  practiced,  ought 
to  be  called  axillary  sympathectomy,  brachial,  iliai,   I'ciiii  ital,  etc. 

L  TechnkjuE.— In  order  to  achieve  it,  u  i^  ii.,,ssai>  to  uncover  the  artery  by  the 
classic  procedure,  open  with  the  bistoury  the  k  llulai  sh,  atli.  separate  the  artery  for  8  to 
10  cm.,  get  hold  iif  the  inner  sheath  directly  wn  tlie  nlsmI  wall,  incise  it,  pull  one  of  the 
lips  tints  itia.lf  wttli  a  l^arc'is,  \r^■^.  it  either  with  the  bistoury  or  with  the  grooved 
proJH.  ,.aii|.N  t<  iv  tiijMiiii:-'  tlir  ait.iy  of  all  the  cellular  tissue  that  adheres  to  it.  More 
or  less  rasiK  a.(>itdiiiL  t^.  tlir  ,  asrs,  i.ne  is  able  thus  to  stri])  the  arterv,  to  decorticate 
a  fold:  thin,  to  I,,,  s„,r,  l.iil  Mit,n  tlii.kei-  tliaii  onr  iiif^lit  .xp.-,  t.  At  a'eerl.ain  moment 
one  has  llie  mipi-rssion  tli.it  o,,,,  ,s  ^,,,im  t.,  traf  tli,'  uall  oi  tli,.  jrtnN  ,  Imt  it"  .nir  pro- 
ceeds ueiitlv  and  laiTtiillN.  euidrd  l.v  tli,  |ioint  ,,l  llir  l,ist,>iii\  ,,r  luol,,-.  ilir  ii-ceing 
process  can  be  earned  on  witliout  risk  ..f  iiij  lit  in..;  llir  ^^.s^l  (  i|ll^  tua,.  |ia\r  I  had 
the  annoyance  of  making  a  small  tear  in  tln'  arte  r\  :  tla  .M.nhiit  was  .Aiilioin  -,iious 
results.  In  case  of  necessity  one  would  fraiikl\  i-csnt  the  s,;oiii  m  oi  ih,  i,  ,n  and  tie 
the  two  ends,  accomplishing  thus  liy  the  same  ait  a  r,  mipk  i.'  s.  iM|ialla  .  t.  nir,  S.  am  times 
the  forceps  removes  only  rather  short  cellnl.ir  fra:anients.  al  otiui  tiiiiv,  oiu  leiiiovca 
quite  definite  lamina',  and  tin-  !iio\  ctneiil  of  freeing  recalls,  oii  a  small  scale,  the  sub- 
serous decortication  of  an  inllamrd  a|i|iendi\,  but  oiir  iu\er  succeeds  in  removing  a 
continuous  layer;  it  is  nerrssar>  to  repeat  tiie  attempt  se\er,il  times  and  with  perse- 
verance to  catch  the  sheath  again,  to  remove  thin  meshes,  and  not  to  slop  until  one 
has  really  the  feeling  of  having  removed  everything.  i\!oreo\ir.  one  can  verify  what 
has  been  done  by  wetting  the  wound  with  a  tampon  soaked  with  \eiy  warm  serum: 
the  artery  takes  on  then  a  whitish  appearance,  looks  as  though  made  of  felt,  and  one 
sees  very  clearly  whether  there  remains  still  some  cellular  debris  more  or  less  detached. 

In  the  course  of  the  cellular  decortication  it  is  necessary  to  be  careful  to  expose 
the  collateral  branches  and  guard  against  tearing  them.  This  happens  sometimes;  by 
using  then  a  forceps  ano  a     -  c   ,gut  one  repairs  this  accident  without  injury 

to  the  artery.  In  addition  to  the  tears,  which  cause  a  spurt  of  pure  blood,  there  may  be 
o(jzing   from  the  tearing  of  the  vasa  vasorum. 

II.  The  I'Hvsiut.ocic.M.  Reaction. — The  operation  thus  done  is  a  physiological  o|)- 
eration ;  I  mean  to  say  by  this  that  it  is  inevitably  followed  by  a  characteristic  physio- 
logical reaction,  which  may  be  regarded  as  the  test  of  the  ol>eration;  as  there  are  char- 


Pagc  KS 


RAXSOHOFf  MHMORIAL  VOLUME 


acteristic  signs  of  the  section  of  the  trunk  of  the  sympathetic  in  the  neck,  so  there  are 
characteristic  signs  of  the  section  of  the  periarterial  sympathetic  nerves.  If  tliese  are 
wanting,  the  operation  has  been  attempted  but  not  acconipHshed. 

The  results  of  our  studies  of  these  signs  Heitz  and  I  have  reported  to  the  So- 
cicte  de  Biologic  ;*  they  are  as  follows : 

Primary  Siqn. — When  one  touches  the  sympathetic  sheath,  the  artery  contracts . 
it  is  reduced  progressively  in  size  to  the  point  where  it  is  not  more  than  a  third  o'- 
even  a  fourth  the  normal  size  throughout  the  whole  extent  of  the  denuded  segment. 
The  segments  on  both  sides  maintain  their  normal  size  provided  the  operation  has  not 
injured  them.  The  phenomenon  is  more  or  less  rapid  according  to  the  case;  certai'-. 
individuals  appear  to  have  more  irritable  sympathetic  nerves  than  others;  their  arteries 
diminish  in  size  at  the  first  touch ;  with  some  the  contraction  is  sluggish.  One  cannot 
yet  give  the  real  reason  for  these  variations.  Furthermore,  the  contraction  is  more 
marked  in  the  brachial  than  in  the  axillary  and  the  subclavian  :  it  is  slower  in  the 
femoral  than  in  the  brachial,  and  less  intense  in  the  common  iliac  than  in  the  femoral. 
In  a  word,  the  contraction  is  stronger  in  the  arteries  of  small  size  than  in  the  large- 
trunks 

This  arterial  contraction  habitually  causes  the  pulse  to  disappear,  liut  it  does  not 
altogether  interrupt  the  circulation. 

Secondary  Signs. — In  the  following  hours  the  pulse  is  imperceptible  or  very  feeble 
and  the  limb  is  colder  than  the  other.  Then  little  by  little,  at  the  end  of  three  hours, 
six  hours,  and  most  often  after  twelve  or  fifteen  hours  there  appears  the  characteristic 
I'hxsidlofiical  reaction,  the  establishing  of  which  ought  to  he  exacted  as  proof  that 
suppression  of  the  sympathetic  nerves  has  been  properly  done. 

This  reaction  is  characterized  )-,y  an  ele\atinn  of  the  local  temperature  reachin.g 
to  2°  and  even  3°  [centigrade],  by  the  elevation  of  the  arterial  pressure,  and  by  the 
augmentation  in  the  amplitude  of  the  oscillations  of  Pachon.  M.  Heitz,  who  with  his 
very  special  competence  has  established  these  facts  many  times  on  my  patients,  has 
found  that  the  increase  in  pressure  could  be  as  much  as  4  cm.  of  mercury  in  compari- 
son with  the  healthy  side  (method  of  Riva  Rocci)  :  it  is  a  detail  worthy  of  mention 
that  analogous  figures  were  noted  by  Claude  Bernard  in  his  investigations  of  the 
cervical   sympathetic  nerves. 

This  vasodilator  reaction  is  only  temporary :  the  hyperthermia,  the  rise  in  pressure, 
and  the  increase  in  amplitude  of  the  oscillations  diminish  little  by  little;  sometimes  as 
early  as  the  15th  day  and  usually  at  the  end  of  a  monlli  i'u  "n  i~  it  n  i  more.  On  the 
other  hand,  in  some  cases  in  which  I  have  performed  -m  ii  the  brachial 

or  the  subclavian  artery  by  resecting  totally  the  nlililer.,'  ird,   the  eleva- 

tions of  temperature  have  been  more  lasting  than  in  tlu  .  i-  -  n  \' In  h  a  sympathec- 
tomy by  denudation  alone  was  done.  This  is  comprehensible,  for  the  operation  is  more 
complete — the  sympathectomy  being  necessarily  total.  Classed  with  these  observations, 
should  he  one  made  by  M.  Babinski  and  M.  Heitz  :  four  months  after  the  extirpation 
of  an  axillary  aneurism  the  hand  on  the  side  operated  on  was  frequently  warmer  than 
that  on  the  healthy  side.  This  phenomenon,  apparently  paradoxical,  is  understood  very 
well  when  one  considers  that  the  ablation  of  a  sac  is  in  reality  a  total  sympathectomy. 

III.  The  Lessons  Furnished  by  the  OpEr.vtion. — Observation  of  series  of  opera- 
tions and  analysis  of  the  therapeutic  results  permit  interesting  deductions  from  physio- 
logical and  pathological  points  of  view. 

1.  I- row  the  Pliysiological  Point  of  I'ic-a'. — Two  facts  become  clear:  the  vaso- 
motor phenomena  which  Heitz  and  1  have  studied  under  the  name  of  va,sodilator  re- 
action permit  us  to  isolate  the  paths  along  which  certain  vasoconstrictive  acts  are 
conducted  and  to  establish  their  correct  value. 

But  there  is,  above  all.  this  one:  it  seems  to  follow  from  certain  observations  that 
the  voluntary  muscular  contraction  is.  in  a  certain  sense,  very  dependent  on  the  sym- 
|)athetic  nerves.  The  integrity  of  the  motor  nerve  and  of  the  muscle  are  not  sufficient 
to  insure  the  proper  accomplishment  of  the  movement  that  is  commanded.  If  the 
sympathetic  nerve  is  affected  at  a  distance,  or  if  it  does  not  act  normally,  the  muscle 
becomes  hard,  and  contracts,  and  the  will  is  powerless  to  relax  or  contract  it.  Now 
in  these  cases  sympathectomy  lifts  the  barrier  and  makes  possible  the  progressive 
reparation  of  the  voluntary  movements.  In  the  case  of  wounded  men  having  reflex 
contractions  of  the  Bahinski-Froment  type,  with  fingers  twisted,  motionless,  incapable 
of  movement,  it  has  been  sufficient  to  modify  the  vasomotor  innervation  to  see  a  cer- 
tain degree  of  voluntary  motion  appear  again  the  following  day. 

This    fact    which    M.    Heitz-''    and    I    have    confirmed    several    times    has    a    rea! 


Des    effet! 

Iherminue  et  hyptrtension 

locales). 

SLeriche    and    Heitz: 

Influence 

segment  aileriel  oblitere  s 

ur  la  contra 

pliysiologii]ues    de   la    sympathectomie    periphcrique    (r 
".   R.  de  la  Soc.  de  Riol..  20  Janvier.   1917. 
[le    la    sympathectomie   periarterielle    on    de    la    resectio; 
■lion  volontaire  des  muscles.     Societete  de  Riologie.  17  1 


WILLIAM  S.  HALSTED 


physiological  bearing.  What  we  now  know  of  muscle  inner\ation  in  man  docs  not 
lead  us  to  suppose  that  it  is  a  matter  of  a  directly  muscular  actii>n.  It  appears.  ur*il 
we  have  made  further  inquir\.  thai  the  \  a^' mii  iti.i  iihim  iimii.i  .il.nc  are  concerned  in 
it,  and  a  fact  which  would  tend  i.i  pr^v.  tins  is  ili.ii  ili.  utiiiii  .ii  ni^.tdity  coincides 
with  the  appearance  of  the  p. isi  Mip.r. uu  c  \  .isodilaP  ii-  ir,Hii..ii  i  tlial  is  Ici  say.  the 
warming  up  of  the  muscle,  its  new    rirciilut.iry   system  i,  and   ImH.iws  the  course  of   it. 

Sympatlicctnmy.  furthcrmnre,  would  appear  to  establish  the  fact  that  the  sympa- 
thetic ncr\e  is,  in  man,  the  excildsecretory  nerve  of  the  sweat  glands:  1  have  seen 
l)ri..fuse  sweatinL;  ..f  the  hand  disappear  after  svmpathcctomv.  The  nerve  prn1)abl\ 
also  inllu.nces  the  i;r.,wth  ..f  the  nads  and  the  tr,.phirilv  ..I'lhc  skin,  s.nce  In.phi.- 
phen.inu-.i.a  drsappear  rapi<llv  aft.^r  s\  mpalbrrt.  .nn  Th.^  lUM-vcs  ,,t  llie  rn^^brnspinal 
sxste.n,   fr.im  this  p.iiiil   .it    \iew  :nv  pn.l.aMv  .,n]v  ihr   NrrLns  ,,t'  tin-  sMupathrtir 

1.  [■rum  Ihc  rutnl  of  I'lcw  of  I\illio/,:,iica/  riixsiolo,/y.  Sympathectomy  is,  in 
certain  cases,  a  true  method  of  experimental  analysis  for  the  interpretation  of  certain 
complex  phenomena. 

It  demonstrates:   fa)   'I'hr  Inic  iiwi-haiiisin 

arteries.     Spont;incoP     1 I.'-,    wluii   an   :r 

jectile.  is  ccrl,iinl\  -■'.''  '  '  :  i.  d  \,\ ,  1 1'  it  i 
the  artery  wlin  h  l.^ll.  ■  i!-  .i.  n  in  lion  oi  i 
pared  to  the  consnln  .1.'.  .i-iniiinr-n  n  f  r.dibre 
Since  a  brachial   ,irii  r\    is   reiluced  to  the  size 

sympathetic  nir\r  is  rxrisrd,  it  is  easy  to  comprehend  how  sponlaiuous  liemostasis  i.^ 
possible  after  .  rrt;iiii  ui.iinds  of  the  arteries  which  are  ineMl:dil\  accompanied  In- 
tearing  of   the   sliealli 

fill  Tin-  r.al  ^nifinr  of  o.-rtaiii  o,iii.uih/i„.s:  if  not  of  all.  As  1  diiiiotisi  r.ili.l  to  the 
Sociele  dc  XniioloLiie,  :n  l;innai\.  I'di.  one  ran  cure  obstinate  cans.i'ui.o  In  r  oisinL; 
the  imolvnl  s\  nip.illictic  inr\c  'I'liis  oliser\  :ition  proves  the  svmpallini.  on^in  ,.i  th  ' 
violent  pains  uliuli  :irronip,iii\  .rinnn  uoiinds  oi  nrr\rs  In  th.-s,-  r.isr,  tlir  |.iiii  phe- 
nomena are  iioi  .liir  to  tlir  iirrM-  l,',io,is.  Im  to  ih,  l,s:,,„s  ,,f  ili,  ,i,rJil,o,-iii.^  svm- 
pathetic    nerve    l  tlu-    pcrnasruhir    s\  mpallirti.     of    tin-    hixirlnal  ,     or    ,,i    ilir    ml  i.i-iierve 

arterv).     This  explains  ilir   fact  ,irmoiis|ratrd  bv  .\l.   rirrrr  M.inr,   M     Mu^r  and   Mme. 


of  the  frndnc-ti, 

s  ii:,i    .iitirrK    d 

,„  of  dry  , 

or    deslrov 

llr    to,    tllr  ■ 

voinids  of  th 
,ed    by    a    pro- 

uhull    is    olisrrv 

of  a   radio-palm 

lar  .".r  :i   di 

may  be  com 
mpathectomv 
i^ital  when  it< 

which   have  :iii  .irlcrx    of  tlinr  own  or  uhicb  are  close  to  a  laryc  arterv.     Tins   fact  is 
now  adnntted   by   tlu'  iieiiroloyists 

(c)  Thr  rri-y  oiool  role  of  III,-  syoi f'athctic  in  the  production  of  the  reflex  con- 
tractuoii  of  l'o}loiist^i-l' roiiu-iit.  l.ei  its  pay  attention  to  the  characteristics  of  this 
ty[ie  alioiit  which  there  is  so  miub  ci infusion.  I  speak  now  of  the  true  Babinski-Fro- 
ment  type,  that  in  which  the  vasomotor  and  thermic  phenomena  are  associated  with 
motor  disturbances  and  with  modifications  of  the  mechanical  excitability  of  the 
muscles. 

Tn  the  cases  of  (his  kind,  studied  liv  \I  I'.abinski  or  bv  his  assistants,  bVoment  and 
Heit?,  1  Ikivc  s,.en  wilb  Heif  iiioi,,i  d.sinrb.ntres  dis:,p|,e:ir  :ilmost  ronipletelv  after 
svmpatbertomv.  brom  the  do  toPouin^  the  o,Hr,,!ioti,  wli.n  ll.e  x,,sodih.tor  reaction 
was  very  well  ,s|al-bsl„Ml.  the  teolnlii^  leliinied  tninkedlv  in  bands  fixed  immutably 
in  positi..n,  <onli,iei,d,  the  htiL^eis  lieing  bent  into  the  palms,  or  else  turned  back  on  the 
dorsal  side.  1  am  in.  lined  lo  lielie\e  that  a  number  of  these  severe  cases  are  referable 
to  distinb.inees  of  s\  iii|,alliei  a  onuin,  caused  by  the  imprisonment  of  the  nerve  ends  in 
a    hard    and    conipressmi;    ,tr..iiix 

(d)  The  role  of  the  .<;v<nhilhclu-  in  the  f^rodiutioii  of  ocrlaiu  ./riffes  cnlutale.;. 
.After  brachial  sympathectomx  I  li.ne  seen  ;i  looseiiine  up  of  a  \er\  rii^i.l  uriffc  eidjitale 
which  had  resisted  resection  ;iiid   snuire  of   the  iierxe   dnided   in   the   forearm. 

I  have  made  this  observation  only  once,  but  the  phenomenon  was  perfectly  definit.-. 
It  seems  to  me  that  the  observation  should  be  recorded  because  of  its  therapeutic  in- 
terest. 

(e)  The  role  of  the  synipathrtic  in  the  cxflanation  of  thn.<;e  motor  paralysis,  more 
or  less  complete,  zvhich  foil..:.  ,,-',,'o  ,,o ',;;,,'  ,',.,:.-,,o  Wlen  the  nerves  have  not 
been  disturbed,  we  call  it  is.l  ;a  ;.  ■  I  a.  i  : '  i  ,  |i;  .  'l,iiion  an  entirely  dif- 
ferent sense  from  that  wbali  ■.  '•  ■  .  an-l  i  a  '!a  .  lOaj  contracture  of  the 
flexors  of  Volkmann.  Tn  ila  ■  ,-  -'.  ,i  ',.]  ',  \|\l  h,  .,.n,-  and  Tinel  there  is 
rather  complete  motor  par.aKsi-  \\\[\,  the  reailion  ,,i  il.ai  leiaii  a  ai,  \  i-t  the  nerves  were 
not  divided.  The  p:irahs,s  eona  i.les  willi  ,.ii  oaleni.iloiis  in  hit  i  aalton  .,f  the  hand  with 
marked  vasomotor  disi  n,  1 ,  la  .  .  ,^  bieli  lead  to  t  lau  lilaons  transformation  of  the 
band.  At  the  end  oi  s,,n,e  weeks  ibe  uaUnia  begin.s  to  .liminish.  the  tendons  and  the 
apcmcuroses  are  ensbe.iled  in  a  \eiii.ilile  fibrous  envelope;  the  muscles,  alreadx  hard  an<l 
tense,  retract  and  take  on  a  l;L.'iie,ais  lonsistency.  In  this  picture  is  seen  the  mark  of- 
the  sympathetic;   and   m    domi;    s.\  iiipalbectomy  in   these  cases   M.   Heitz  and    I    have 

Page  J'n 


RA.VSOflOFF  MEMORIAL  fOLUME 


seen  vasomotor  disturbances  disappear,  trophic  disturbances  improve,  tlic  tendons  and 
the  muscles  become  on  palpation  sensibly  more  supple,  and  the  muscles  execute  slight 
movements.  In  one  case,  although  before  operation  there  had  been  complete  degener- 
ative reaction,  four  months  after  operation  we  observed  a  very  definite  amelioratioii 
of  the  electric  reactions,  and  we  are  hoping  for  a  marked  functional  recuperation. 

I  do  not  wish  to  say  that  sympathectomy  cures  the  patients ;  and  it  is  impossible 
that  it  should  cure  them  at  once  when  one  considers  their  wounds.  Unhappily,  there 
is  no  cure,  but  to  me  it  appears  to  have  caused  the  disappearance  (at  least  momentarily) 
of  the  stiffness  of  the  muscles  and  tendons;  it  has  assured  a  manifest  suppling  up  of 
muscles  which,  after  the  sympathectomy,  executed  movements  equivalent  to  one-half 
the  normal.  Referring  to  the  fact  mentioned  above  a  propos  of  griffe  cubitalc.  I  have 
the  impression  that  the  sympathetic  has  an  enormous  influence  on  the  evolution  and 
production  of  fibrous  tissue.  The  sclerous  evolution  is  modified,  it  appears,  when  a 
vasodilator  reaction  is  brought  about.  Whence  the  conclusion  that  the  sympathetic 
plays  probably  a  large  role  in  the  mechanism  of  the  so-called  ischemic  paralysis  wher> 
the  predominating  feature  has  not  the  mark  of  ischemia.  I  do  not  mean  to  say  that 
the  circulatory  suppression  caused  by  the  arterial  lesion  does  not  play  any  part,  that 
would  be  absurd :  what  I  would  say  is  that  something  more  is  involved.  But  these 
cases  are  too  rare  in  general  surgical  practice  for  me  to  follow  the  analysis  alone. 

(f)  The  role  of  the  symfalbctic  iu  the  I'rodiictioit  of  heel  sloiiglis  in  the  course 
of  mednUary  lesions.  In  one  patient  who  had  had  flabby  incomplete  paralysis  of  the 
lower  limbs  with  absence  of  reflexes,  and  incontinence  of  urine,  there  were  two 
sloughs,  one  on  the  heel,  the  other  on  the  little  toe.  They  resisted  all  treatment.  Three 
months  after  the  wound  had  been  received,  a  femoral  sympathectomy  was  done.  Three 
days  later  the  ulceration  of  the  toe  was  dry  and  cicatrized:  that  of  the  heel,  which  was 
as  large  as  a  small  palm  of  the  hand,  diminished  in  size  and  was  covered  with  active 
granulations.     In  thirty-five  days  it  was  completely  cicatrized. 

3.  From  the  Therapeutic  Point  of  View. — I  have  tried  sympathectomy  in  a  great 
variety  of  cases,  and  it  is  rather  difficult  for  me  to  analyse  the  results,  because  there 
were  often  complex  situations  to  be  dealt  with.  Schematically,  1  have  tried  to  influ- 
ence the  element  of  pain,  the  element  of  reflex  contraction  with  vasomotor  dis- 
turbances, and  the  trophic  element.  In  all  the  cases  I  have  had  failures  and  disap- 
pointments. 

I  have  done  sympathectomy  eleven  times  for  phenomena  of  pain  :  ^once  the  vaso- 
dilator reaction  failed.  This  operation  was  badly  done  and  I  elimina'te  it.  For  the 
ten  others,  six  times  there  were  true  causalgias,  and  three  times  phenomena  of  pain 
more  or  less  intense. 

For  cau.mlgia  I  operated  four  times  on  the  upper  extremity,  twice  on  the  lower 
limb.  The  four  cases  in  the  upper  extremity  resulted  as  follows :  One  complete 
failure  (patient  operated  on  in  the  service  of  M.  Gosset").  two  excellent  results  f com- 
plete suppression  of  the  pains,  total  transformation  of  the  patients')  with  final  cure, 
now  dating  back  19  and  16  months.  These  two  patients  have  been  discharged,  and  are 
earning  their  living  exclusive!)'  by  their  own  work. 

In  a  fourth  case,  which  was  very  serious,  I  had  found  the  brachial  artery  ob- 
literated. I  had  not  at  the  time  thought  that  there  would  be  any  advantage  in  re- 
.secting  the  obliterated  segment.  I  performed  then  a  sympathecomy  by  denudation 
The  patient  w'as  much  improved  :  he  who  for  months  had  been  confined  to  his  bed  with 
a  wet  cloth  on  his  hand,  apprehensive,  indifferent  to  everything  except  his  pain,  got 
up  and  submitted  to  the  same  regime  as  his  comrades :  but  some  pains  persisted.  Tn 
order  to  improve  these  I  again  took  the  patient  under  my  care  and  resected  the  ob- 
literated arterial  segment,  whereupon  the  persisting  disturbances  almost  completely 
vanished  :  this  result  promises  to  be  permanent." 

In  the  lower  limb  I  did  one  femoral  sympathectomy,  with  appreciable  ameliora- 
tion. At  a  second  operation  I  resected  the  sciatic  artery  and  the  artery  of  the  sciatic 
nerve,  with  manifest  result,  but  the  cure  has  not  been  complete.  The  patient,  who  has 
been  followed  for  six  months,  is  entirely  relieved  at  certain  times,  but  has  suffered  much 
at  others  in  damp  weather.  His  general  condition  is  transformed.  For  those  who  know 
the  lamentable  condition  of  degeneration  of  these  patients  caused  by  their  martyrdom 
of  pain,  the  words  "great  amelioration"  have  a  real  significance.  This  expression  should 
not  be  taken  as  a  euphemism  masking  a  failure. 

In  another  case  I  did  a  common  iliac  sympathectomy,  which  resulted  in  great 
improvement  [grande  amelioration!  with  complete  transformation  of  the  general  con- 
dition. The  patient  has  suffered  at  certain  times,  but  his  days  of  respite  have  been 
greater  in  number  than  his  days  of  pain.  This  is  also,  to  my  thinking,  a  success  worth 
trying  for. 

6.  Tn  one  of  the  last  Bu'lnins  of  the  Socu'lc  de  Chirureie  a  very  intL-resliiiK  observation  by 
M.  Le  Temtpl  is  reported,  which  shows  well  the  rnle  of  the  sympathetic  in  the  paretic  syndrome  fol- 
lowing an  obliteration  of  the  brachial. 


WILLIAM  S.  HALSTED 


For  all  "causalgiqiies"  the  question  is  complex  in  other  ways:  these  patients  have 
a  psychology  of  their  own  ;  it  is  necessary  to  isolate  them  somewhat  and  to  exercise 
over  them  a  little  authority  if  we  desire  to  cure  them.  Besides,  they  are  extremely 
sensitive  to  atmospheric  changes,  and  it  seems  as  if  their  whole  vasomotor  system  were 
out  of  equilibrium.  One  local  operation  could  not  pretend  to  set  all  this  right  at  once, 
and  these  patients  should  not  be  regarded  exactly  as  others. 

I  have  operated  four  times  for  fhenomena  of  pain  accomfanying  vicrvc  lesions  or 
arterial  obliterations.     I  had  three  excellent  results  and  one  complete  failure. 

To  sum  up,  in  the  treatment  of  the  phenomena  of  pain,  sympathectomy  cures 
entirely  certain  patients,  acts  very  favorably  in  the  majority  of  cases,  but  does  not  suc- 
ceed always  or  always  give  an  absolutely  perfect  result. 

Five  sympathectomies  for  trof'hic  ulcerations,  with  or  without  phlycten;e  in  the 
neighborhood,  gave  success  five  times- 

I  have  operated  three  times  for  large  bluish  oedemas  of  the  limbs,  with  one  com- 
plete success ;  one  great  improvement,  followed  at  the  end  of  several  months  by  com- 
plete cure:  one  incomplete  result  with  partial  return  (in  the  lower  limb),  but  on  the 
whole,  amelioration. 

For  reflex  disturbances,  eighteen  sympathectomies  among  the  patients  examined 
heretofore  (except  two)  either  by  M.  Babinski,  or  by  his  assistants  M.  Froment  and 
M.  Heitz,  and  all  followed  up  by  M.  Heitz.  have  resulted  as  follows:'' 

Three  cures,  practically  complete,  traced  for  several  months,  with  disappearance  of 
the  vasomotor  disturbances  and  of  the  contraction  ; 

Ten  ameliorations  more  or  less  considerable,  some  of  which  were  almost  cures: 

Two  ameliorations  followed  by  incomplete  return  in  patients  who  had  not  received 
any  post-operative  treatment.     In  the  two  cases  the  lasting  benefit  has  been  real  : 

One  case  in  which  the  operation,  after  failure  of  all  other  treatments,  has  been 
followed  by  the  execution  of  voluntary  movements:  :iKm,  thanks  to  trciitment  followed 
regularly  under  the  direction  of  M.  Heitz,  motilit\   i^  utiii  iiiiil;  hitli-  by  little: 

Two  complete  failures.  In  these  two  patients  tlnre  had  Ih-iii  alter  operation  a 
beginning  return  of  voluntary  motility,  but  the  therapeutic  result  has  been  practically 

In  all  the  patients  who  have  been  really  benefited  by  the  operation  (16)  the  vaso- 
dilator reaction  has  been  followed  by  a  diminution  of  the  contraction  and  by  a  reap- 
pearance more  or  less  complete  of  the  voluntary  movements.  In  some  cases  the  result 
has  been  surprising  :  from  the  day  following  operation  the  patients  were  able  to  make 
movements  which  had  been  impossible  for  months.  But  at  the  end  of  two  or  three 
weeks,  as  the  vasodilator  reaction  subsided,  the  contraction  shows  signs  of  beginning 
anew  and  the  movements  diminish  in  amplitude.  Observing  this,  we  thought,  with 
M.  Heitz,  that  the  maintenance  of  heat  in  the  member  operated  upon  was  indicated. 
For  this  purpose  M.  Heitz  has  made  my  patients  take  baths  of  paraffine  at  60°  for  about 
one  half  hour.  By  associating  with  this  treatment  massage  and  re-education  Heitz 
has  obtained  very  interesting  results,  which  permit  us  to  speak,  in  certain  cases,  of  true 
cure. 

Briefly  then,  in  the  grave  forms  of  the  syndroine  of  Babinski-h'roment  sympa- 
thectomy by  itself  does  not  suffice.  But  without  it,  the  treatment  usually  applied  soon 
ceases  to  influence  the  condition,  and  the  result  becomes  stabilized  :  the  operation,  like 
so  many  other  operations  upon  the  nervous  system,  leaves  room  for  and  facilitates  re- 
education, and  gives  to  it  its  eflicacy.  It  is  only  one  phase  of  the  treatment,  but  it  is  a 
very  rewarding  phase.  1  insist  on  this  point  so  that  we  shall  not  expose  ourselves  to 
failures  ail  the  more  bitter  when  the  operation  at  the  outset  promised  to  yield  a  bril- 
liant result.  -\nd  1  recall  what  Heitz  has  recently  written  :*  it  is  the  mixed  method 
(operation  on  the  sympathetic  followed  by  the  treatment  indicated  above)  which  has 
given   in  the  scr\icc  of   M.  Babinski  the  best  results. 

/■'())•  thr  paralyses  connected  unth  vascular  obliterations,  associated  or  not  with 
nerve  lesions,  sympathectomies  have  improved  the  criii.lition  without  giving,  except  in 
one  case,  a  true  functional  result.  In  such  case  the  s\  iii|iailu<  lomy  sliould  lie  done  to 
modify  the  vascularization  of  the  paralyzed  segment,  to  clmk  the  libroiis  regression  of 
the  muscles.  It  cannot  constitute  of  itself  a  sufiicient  Ireatnunt,  but  it  has  appeared  to 
me  to  be  interesting  and  useful.     The  future  will  determine  its  indicalion. 

7.  'J'lie  observations  will  lie  piiltHslu.l  m  twlcn.so  in  the  .^ul^u^l  iuuiiIm  i  <a  /.yon  cltiyiirqical . 
under    the    fotlowint    title:      Resultuts    de    la    synipatbectomie    IJere-ai  IcuLilc    tiaiis    Ic    traitcmenl    des 

traumatiques  d'ordre   reflexe.     Archives  des  maladies  du  coeur,  Avril    1917,   ii.    160. 


RAXSOIlOI'f  MEMORIAL  WILUME 


It  is  the  same  In  regard  to  the  value  of  sympathectomy  associated  with  operations 
upon  the  nerves  in  cases  of  rebeUious  contracture  of  the  median  or  of  the  ulnar  nerve 
variety.  One  cannot  say  definitely,  but  the  question  appears  to  me  to  merit  consid- 
eration.!* 

In  order  to  estimate  the  results  of  sympathectomy  1  have  striven  to  be  as  concrete 
as  possible:  I  have  appraised  as  nil  any  result  which  was  without  value  for  the  patient. 
The  verdict  may  perhaps  appear  to  be  very  reserved.  Truly,  I  believe  that  the  opera- 
tion is  a  very  interesting  one  and  a  useful  expedient  to  which  one  may  resort  in  cases, 
very  diverse,  which  have  been  irresponsive  to  all  other  treatments  :  but  it  remains  for 
us  to  define  clearly  the  indications  for  it. 


9.      Recently   T   tried   to  arrest,   by   sympatliecto.ny.   the  appearance  of   t 

;an>:renc   aft. 

Ihe  popliteal  vessels.     The  operation  was  followed  by  complete  d.sappearani 

the  hue  of  the  violet-colored  spots  which  covered  the  limb.      For  36  hours 
result,  but  none  appeared,  and   I   had   to  amputate  the  thigh. 

THE  PATHOLOGY  OF  CHROMIDROSIS.* 

M.  L.  HEIDINGSFlil-D.  Ph.  P...  M.  D. 

Cincinnati. 

The  name  chroniidrosis  imphcs  an  anomalous  secretion  from  the  sudori- 
ferous or  sweat  glands  characterized  by  colored  perspiration.  Its  occurrence 
is  exceedingly  infrequent ;  Foot.'  in  a  careful  review  of  the  lierature  dating 
from  1709  to  1868,  has  been  able  to  enumerate  but  38  cases,  to  many  of 
which  a  doubtful  character  must  necessarily  be  attributed.  Fowie's-  careful 
historical  review,  1709-1891,  does  not  add  many  well-defined  cases,  and 
surprisingly  few  have  been  reported  in  the  literature  of  recent  years.  Its 
marked  infrequency  can  be  best  a])preciated  by  referring  to  the  \'an  Har- 
lingen's-''  statement,  that  "it  is  so  rare  as  to  be  a  curosity  rather  than  a  dis- 
ease." 

Those  who  have  written  on  the  subject,  almost  without  exception,  are  of 
one  accord  as  to  nature,  and  attribute  to  the  condition  a  disorder,  functional 
or  otherwise,  of  the  sweat  glands.  This  is  especially  evident  in  all  the  text- 
books of  skin  diseases,  where  the  sulijects  are  not  alphabetically  arranged 
and  follow  some  system  of  classification  (  Hyde.*  Hardaway.''  Morrow," 
Kaposi,'  Duhring,^  Joseph,"  Stehvagou,'°  Shoemaker,'^  Schamberg,'^ 
Fox,'^  Gottheil,'*  etc.)  ;  in  these  the  affection  is  invariable  classed  with  th;; 
anomalies  of  glandular  secretion,  namely,  the  sudoriferous  glands,  and  i.-; 
grouped  with  hyperidrosis,  anidrosis,  bromidrosis,  uridrosis,  hematidrosis, 
etc.  In  those  which  follow  an  alphabetic  arrangement  an  anomaly  of 
secretion  is,  as  a  rule,  directly  attributed,  or  indirectly  implied  (Jackson,'' 
\'an  Harlingen,'"  etc.),  apparently  a  few  (Lesser,'"  Mracek,"  Bulkely,'" 
Neumann,^''  etc.),  studiously  refrain  from  committing  themselves.  It  is 
surprising  that  some  of  the  earliest  observers  ( Nelligan,  Wilson  and  Gin- 
trac)  have  attributed  the  condition  to  a  stearrhea,  and  Turenne  to  a  metas- 
tasis of  the  eye  pigment,  facts  which  seem  not  so  remarkable  when  we  con  - 
sider  that  the  early  investigators  were  very  keen  obser\ers  and  relied  alinost 
exclusively  on  their  powers  of  personal  observation. 

The  color  of  the  secretion  varies  with  different  cases,  green,  blue,  purple, 
black,  brown,  yellow,  red  and  intennediate  shades.  Black  is  the  most 
common,  occurring  is  one-half  the  cases  reported  by  Foot.  Cases  character- 
ized by  red  pigmentation  are  generally  associated  with  a  reddish  incrusta- 
tion of  the  adjacent  (usually  axillary)  hairs,  the  bacteriologic  examinatioii 
of  which  reveals  the  condition  to  be  due  to  a  Zooglea  (Bacillus  prodiyiosus) , 
which  grows  in  rose-red  colonies  and  often  gives  a  history  of  direct  con- 
tagion. These  cases  cannot  be  properly  classed  with  the  so-called  chromidro- 
sis,  but  belong,  by  nature,  with  greater  propriety  to  the  class  of  so-called 
vegetable  parasitic  afTections  of  the  skin. 


•  Read 

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Bauni. 

♦  From 

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sociation. 

December 

1 

RAXSOHOFF  MFMORIAL  VOLUME 


In  my  own  clinical  and  private  practice  I  have  noted  eight  cases  of  this 
so-called  red  chromidrosis  during  the  past  two  years,  in  most  of  which  there 
was  not  only  a  reddish  discoloration  of  the  incrusted  hairs,  but  also  distinct 
reddish  discoloration  of  the  superimposed  garments.  If  this  class  of  cases 
is  included,  chromidrosis  is  by  no  means  a  rare  affection,  and  it  probably 
falls  to  the  lot  of  nearly  every  close  observer  to  note  these  cases  from  time 
to  time.  At  present  I  have,  among  others,  two  patients  under  observation 
with  this  form  of  affection,  an  uncle  and  nephew,  the  latter  of  whom  is  a 
practicing  physician,  who  has  taken  up  his  residence  with  his  uncle  during 
the  past  four  years.  The  physician  states  that  his  infection  is  of  five  years' 
duration,  and  that  his  mother,  with  whom  he  then  resided,  is  similarly  af- 
fected, and  has  had  her  affection  for  almost  the  same  length  of  time.  His 
uncle  acquired  the  affection  almost  four  years  ago.  and  more  recently  hi.s 
daughter  has  also  been  infected.  The  axillse  in  all  the  cases  have  been 
involved,  and  all  the  cases  show  tiie  red  discoloration  to  a  marked  extent. 
From  these  and  other  cases  in  the  literature  it  is  clearly  evident  that  these 
forms  of  reddish  discoloration  are  readily  contagious,  and  owe  their  cause 
to  a  local  infection,  entering  from  without.  Their  parasitic  nature  is 
further  evidenced  by  the  fact  that  some  of  my  cases  of  so-called  red 
chromidrosis  have  readily  yielded  to  a  few  applications  of  \\ilkinson  oint- 
ment. 

Though  nearly  all  who  have  reported  cases  of  red  chromidrosis  have 
attributed  the  cause  to  a  parasite,  dift'erent  authorities  vary  as  to  its  true 
nature.  A  few  (Labrares  et  Cabannes'^j  strongly  deny  its  bacteriologic 
nature ;  Temple-^  attributes  it  to  the  ingestion  of  potassium  iodid ;  Stott,-^  to 
toruL-e,  which  grow  in  rose-bed  colonies  on  potato  culture  at  38  C,  and  deep 
red  at  O  C  ;  Fowie'*  ascribes  the  cause  to  theBacillius  prodiglosus ;  Babesiu^"' 
to  a  form  of  Zooglea,  and  Hartzell-"  to  a  fungus  bearing  a  resemblance  to 
the  Micrococcus  tetragenus.  This  marged  diversity  of  opinion  induced  me 
to  make  culture  experiments  on  potato,  gelatin,  agar.  etc.  Potato  cultures 
served  the  best,  and  though  contaminations  were  very  common,  involving 
diflferent  forms  of  sarcina,  staphylococci  and  bacilli,  deep  brick-red  colonies 
could  be  isolated  in  most  instances,  whose  microscopic  appearance  was  .1 
Micrococcus  tetragenus.     Inoculation  experiments  were  not  attempted. 

Let  us  now  digress  from  the  so-called  cases  of  red  chromidrosis  and 
resume  with  the  more  well-defined  cases,  in  which,  according  to  Foot.-'  34 
out  of  38  were  women,  19  out  of  29  were  unmarried,  age  varied  from  5  t ) 
57  years,  average  being  22  years ;  the  face,  particularly  the  eyelids,  is  most 
commonly  involved  and  uterine  disturbance  and  hysteria  are  frequently  as- 
sociated. In  nearly  all  the  cases  the  attack  comes  on  suddenly  without  ap- 
parent cause,  and  persists  usually  for  a  few  years  in  intermittent  form. 

The  case  which  I  wish  to  report  occurred  in  H.  O.,  a  brunette,  a  native  of  Germany, 
aged  53,  a  merchant  of  intelligence,  good  social  standing,  who  had  been  married  for 
fifteen  years  and  is  the  father  of  one  child.  His  general  health  has  been  excellent;  in 
1898  he  suffered  with  an  attack  of  hepatic  colic,  which  was  followed  by  jaundice,  and 
ihe  following  year,  under  severe  medication,  involving  salivation,  he  passed  a  large 
Patic  lii> 


71/.  L.  IIEIDINGSPliLD 


number  of  gallstones.  In  a  short  time  he  regained  his  customary  good  health,  which 
has  been  uniformly  good  since  1900.  In  1901,  he  noted  for  the  first  time  that  the  linen 
of  his  right  forearm  became  discolored.  The  discoloration  was  a  yellowish-brown  and 
permanent  in  character,  so  that  it  could  not  be  removed  in  the  process  of  laundering. 
The  discoloration  was  rapid  and  extensive,  so  that  in  two  days'  time  a  new  cuff  or  a 
new  shirt  sleeve  was  very  perceptibly  and  indelibly  discolored.     The  coat  sleeve  lining 


^l& 


.  1.  Hyperkeratosis  in  o 
P  and  P;  in  corium,  P 
(VVinckel,  oc.  2,  obj.  5.) 


shared  in  the  discoloration  to  such  an  extent  that  its  renewal,  for  cosmetic  reasons, 
every  two  months,  became  a  necessity.  The  patient  was  able  to  take  note  of  no  other 
subjective  or  objective  symptoms  of  any  character  whatever.  The  condition  has  per- 
sisted continuously  for  the  past  two  years.  Perspiration  has  not  been  excessive  and  to 
the  patient's  knowledge  but  slight. 

When  patient  presented  himself  for  examination,  for  the  first  time  on  March  5, 
1902,  the  skin  over  the  affected  wrist  was  apparently  normal  ;  there  was  no  evidence 
of  any  intlammaticdi,  and  no  disturbance  of  innervation.  Compared  with  the  skin  else- 
where on  the  li.idy  and  with  the  opposite  wrist,  there  was  a  very  slight,  evenly-diffused 


:/ 


Fig.  2.     Two  circumscribed  accumulalicni 
(VVinckel, 


1,  obj.  ,1 


ium,   P  and   P. 
Pant-   /'.'..■ 


RAXSOIIOPF  MEMORIAL  VOLUME 


pigmentation,  as  if  the  affected  area  had  been  hghtly  bathed  witli  tincture  of  opium. 
!t  remained  unchanged  when  scrubbed  with  pledgets  of  cotton  dipped  in  water,  soap, 
alcohol  and  ether  and  the  pledgets  themselves  took  on  no  discoloration.  Pledgets 
dipped  in  chloroform  removed  the  discoloration  rapidly  and  left  the  areas  thus  treated 
much  \v]i'!<  r  '  ■       -'Id  I  I  i;   ill  llic  surrounding  area. 

K-N.ir    .     '     ■  r  ,  ,     .l:(,wed   reaction    faintly   acid,   no   alliumin,    nn    sugar,   no 

formed'  ^-      ;t>  1020  and  no  indican.    L'.lood  examination  by  Dr.  .\lf  red 

Friedlaii'!<  1     :;     ..   i  ii  ^  -,ir,.'ii..n  from  the  normal. 

An  e.xaminatiun  of  the  secretion,  which  was  collected  on  pure  white  linen,  revealed 
it  to  be  insoluble  in  the  ordinary  solvents,  ether,  alcohol,  water,  glycerin,  xylol,  etc., 
and  readily  soluble  in  chloroform,  imparting  to  the  latter  a  yellovvish-brown  color. 
Hydrogen  dioxid  exerts  no  bleaching  action  on  the  yellow  color.  When  evaporated  on 
glass  slides  it  formed  a  smooth  yellowish  substance,  which  under  the  microscope 
revealed  a  semi-crystalline  appearance,  due  no  doubt  to  the  admixture  of  old.  dried-up 
epithelialcells  and  other  detritus  (  Fig.  5 )  ;  when  previously  filtered,  the  microscopic 
appearance  is  amorphous  and  structureless :  when  the  chloroform  is  completely  evapor- 
ated, the  deposit  retains  a  resinous  character,  readily  taking  the  impression  of  the  finger 
and  showing  with  minuteness  the  folds  and  furrows  of  the  skin,  or  can  readily  be 
etched  by  means  of  a  needle. 


Fig  3.     Circumscribed  ;u .  1'.   witliin   the  rete  malpighi 


The  eliminated  substance  is  unaffected  by  acids  (nitric,  hydrocliluric.  sulpluiric. 
carbolic),  and  fails  to  give  the  characteristic  reactions  for  indol,  indican  and  liile  pig- 
ments. The  negative  character  of  these  reactions  and  the  absence  of  indican  in  the 
urine  is  sufficient  evidence,  I  believe,  to  dissociate  this  affection  from  renal  and  hepatic 
predisposing  influences,  notwithstanding  strong  opinions  to  the  contrary  (Labrare,s,2S 
Hofmann^S)    and  the  pre-existing  liver  disorder  in   this  particular  case. 

On  March  8,  a  small  piece  of  skin  was  removed  from  the  anterior  surface  of  the 
wrist,  near  the  ulnar  border,  central  to  the  area  of  greatest  discoloration,  for  the  pur- 
pose of  microscopic  examination.  It  was  thoroughly  washed  for  one-half  hour  in 
running  water  and  hardened  in  successive  alcohol ;  the  use  of  formalin,  Miiller's  fluid, 
etc.,  was  purposely  avoided,  in  order  not  to  induce  discoloration,  or  to  conserve  the 
mask  pigmentary  changes.  The  preparation  was  imbedded  in 
■  1  in  successive  serials,  and  examined  partially  unstained  and 
Mied  with  polychrome-methylene-blue,  eosin.  hemato.xylin-eosin. 
1,  \'an  (liessen.  thionin.  orcein,  etc.  The  unstained  specimens 
lined  with  polychrome-methylene-blue  (.Unna).  decolorized  with 
111  the  most  interesting  changes. 

ras    first   i-eim-rc(l    in    the   microscopic   appearance    of    tlic 
y  are  found  to  he  normal,  sliowing;  no  cystic  dilation,  n' 


blood, 

celloidi 

and    thereb\ 

hemai' 
and   th 
glyceri 

n  ctluT,   sf,,,- 

.M' 

V    interest 

sweat 

glands :  th 

M.  L.  HEIDINGSFELD 


pigmentary  infiltration,  no  discoloration  and  no  inflammatory  changes.  In 
other  words,  no  pathologic  alterations,  no  structural  variation  from  the  nor- 
mal can  be  detected  in  these  elements,  which,  in  any  manner  or  form  can 
induce,  or  result  from,  a  so-called  chromidrosis  or  colored  sweating.  (Fig. 
5.)  This  finding  accords  with  what  would  l)e  naturally  inferred  from  the 
nature  of  the  pigmented  elimination,  the  latter  being  thoroughly  insoluable 
in  water,  could  scarcely  be  eliminated  by  a  secretion  essentially  watery  ii 
character. 

The  general  appearance  and  structure  of  the  skin  is  almost  normal.  The 
epidermis,  cerium  and  subcutaneous  connective  tissue  are  normal  in  their 
general  structure  and  contour.  The  stratum  corneum,  rete  mucosum,  papilla;, 
capillaries,  ducts  of  the  sudoriferous  glands,  show  no  marked  variations  from 
the  normal.     A  marked  hyperkeratosis  is  present  aniund  the  opening  of  the 


Fig.  4.     Circumscribed  accumulation  of  pigment,   in   curium,    with   a  central   cavernous 
space.      (Winckel,  oc.  1.  obj.  .i.) 

hair  follicles,  and  the  adjacent  stratum  corneum  is  thickened  to  two  or  three 
times  the  natural  size.  (Fig.  1.  Associated  is  the  entire  absence  of  sebace- 
ous glands.  Although  hair  and  their  follicles  were  abundantly  present,  and 
innumerable  specimens  were  carefully  examined,  not  the  vestige  of  a 
sebaceous  gland  was  discovered  in  any  of  the  specimens.  Elastic  fibers, 
though  abundantly  present,  showed  no  marked  variation  from  the  normal. 
Examination  with  the  higher  powers  of  the  microscope  readily  show  the 
presence  of  small,  roundish  yellowish  particles,  which  for  the  most  part 
are  located  in  definite  areas  of  the  specimens.  They  can  be  most  easily 
detected  in  unstained  preparations,  particularly  those  which  have  been  pre- 
viously bleached  with  hydrogen  dioxid,  or  specimens  which  have  been  verv 
faintly  stained  with  polychrome  methylene  blue,  and  decolorized  with  glyc- 
erin ether.  Many  are  located  in  external  lasers  of  the  stratum  corneum. 
exclusively   in  and  around  the   hair    follicles,  and   particularly   those   areas 


RAXSOHOPF  MEMORIAL  VOLUME 

which  show  the  above-mentioned  liyperkeratosis.  The  greater  quantity  is 
distributed  to  the  lower  layers  of  the  epidermis  of  those  areas,  where  the 
pigmented  bodies  are  accumulated  to  form  compact  masses,  occasionally 
show^ing  a  central  cavity  and  often  distinctly  walled  off  from  the  surround- 
ing tissues.  (Figs.  2,  3  and  4.)  The  lower  layer  of  columnar  or  germinal 
cells  of  the  epidermis  of  this  region  show  marked  pigmentation,  pigment 
of  the  same  form  and  color,  as  described  above,  and  contrasting  strongly 
with  the  pale  germinal  cells  situated  elsewhere  along  the  epidermis. 

In  and  around  the  papilke,  extending  for  some  distance  into  the  corium. 
and  in  close  proximity  to  the  hair  follicles,  adjacent  tu  the  pigmented 
germinal  cells  of  the  epidermis,  are  numerous  small  pigmented  bodies,  for 
the  most  part  rolmdish,  but  often  irregular  in  outline  and  retaining  the  same 
general  analog)'  to  the  above-mentioned  pigmented  bodies.     The  latter  cells 


t 


•%: 


Fig.  5.     Showing  normal  condition  of  the  .sudoriferous  glands. 
(Winckel,  oe.  2,  obj.  5.) 

have  an  analogy  to  the  s(j-called  chrcmopliore  cells,  which  are  believed  to 
bear  the  pigment  of  normal  cells  from  its  origin  in  the  cutis  to  the  epidermal 
cells.  They  retain  the  same  localization,  and  apparently  perform  the  same 
function,  the  distribution  of  pigment  from  the  cutis  to  the  epidermis.  They 
differ,  however,  materially  in  certain  characteristics.  They  are  smaller  and 
more  roundish  in  outline,  and  show  no  long  proto-plasmic  processes,  so- 
called  pseudopodia.  by  reason  of  which  these  cells  were  for  a  time  supposed 
to  possess  ameboid  movements  and  carry  the  pigment  from  its  point  ol 
emanation  to  the  epidermis.  Ballowitz'"'  has  been  able  to  demonstrate  that 
the  nerve  endings  penetrate  these  cells  and  envelope  them  thickly  with 
dichotomous  branches,  thereby  precluding  their  movement.  He  had  also 
been  able  to  demonstrate  in  the  scales  of  fresh  herring  that  the  apparent 
change  of  form  is  due  to  the  transportation  of  the  pigment  (which  in  the 
chromophores  is  finely  granular)  within  the  cells.    The  chromophores  there- 


M.  L.  HEIDINGSFELD 


fore  probably  serve  as  mere  "stepping  slones"  or  fixed  carriers  for  the  pig- 
ment in  its  course  from  the  deeper  structures  to  the  surface.  The  pigmented 
bodies  in  chromidrosis  differ  from  the  chromophores  of  ordinary  pigmenta- 
tion, in  that  their  contents  are  not  finely  granular,  but  homogeneous  and 
amorphous,  and  that  they  do  not  decolorize  with  hydrogen  dioxid. 

I  was  unable  to  determine  to  my  personal  satisfaction  the  ultimate 
source  of  the  jjigment  in  chromidrosis.  That  its  source  is  from  some  point 
in  the  cutis  is  readily  apparent  from  the  examination  of  the  specimens,  but 
whether  it  springs  from  lymph  or  blood  vessels,  from  pre-existing  cell 
tissue,  or  what  not,  will  be  equally  if  not  more  difficult  to  determine,  I  be- 
lieve, than  the  present  unknown  source  of  the  pigment  of  the  cutis.  Its  ap- 
parently free  dissenn'nation  in  the  epidermis,  tissue  preeminently  vascularized 


Fig.  6.     Concretion   attaclied   li,  „  ..„ „...  „   .. 

(Oc.  1,  obj.  .3,  Winckel.) 


f  red  cliromidrosis. 


by  lymph,  leads  me  to  concur  with  Moritz  Cohn,^'  that  the  pigment  is  derived 
from  the  lymph  s])aces  of  the  cutis. 

I  regret  that  I  have  been  unable  to  discover  in  my  investigations  into  the 
literature  any  report  on  the  histologic  changes  in  any  of  the  cases  thus  fai 
recorded,  inasmuch  as  a  comparison  would  have  been  of  great  interest  and 
confirmation  of  great  value.  No  mention  of  chromidrosis  is  made  in 
Unna's^-  "Histopathologie  der  Haut,"  a  work  that  is  very  comprehensive  as 
regards  the  pathology  of  the  skin  and  replete  in  all  its  detail.  One  case  is 
hardly  sufficient,  especially  in  a  disease  w^iich  shows  so  many  variations,  to 
serve  as  a  standard  for  all,  but  its  marked  infrequency  precludes  the  reports 
of  accumulated  cases. 

With  the  hope  that  a  spectroscopic  examination  may  have  been  able  to 
shed  more  light  on  the  nature  of  the  eliminated  pigment,  a  chloroform  solu- 
tion was  sent  to  Mr.  C.  P.  Fennel,  who  has  kindly  reported  that  absorption 


RAXSOHOFF  MFMORIAL  J-QLUME 


bands  were  not  present,  and  hence  it  was  not  a  product  of  hemoglobin  or 
oxyhemoglobin.  Sodium  bands,  somewhat  expanded,  were  present,  togethci' 
with  two  faint,  narrow  interposed  lines,  which  could  not  be  read  with  any 
degree  of  satisfaction.  A  careful  chemical  analysis  has  not  been  attempted, 
but  for  reasons  above  stated  I  do  not  concur  that  it  is  derived  from  indigf) 
or  indican,  bile  or  hemoglobin.  I  belie\e.  for  the  present,  it  can  be  classed 
with  due  propriety  with  the  large  class  of  pigments  of  the  body,  the  nature 
of  a  large  number  of  which  is,  as  yet,  so  little  known  and  imperfectly  under- 
stood. I  am  unable  to  attribute  to  my  case  any  direct  or  predisposing  cause. 
He  is  of  a  temperate,  phlegmatic  disposition,  quiet,  unobtrusive  in  nature  and 
had  noted  the  affection  over  a  year  before  he  became  sufficiently  interested 
to  bring  it  to  the  attention  of  a  physician.  Similation  has  been  carefully 
ruled  out  by  applying  a  coating  of  zinc  gelatin  to  the  affected  area,  after  a 


Fig.  7.     Structural  appearance  of  the  concrctiuii  attached  to  a  hair,  taken  from  a  case 
of  red  chromidrosis.      (Oil  immersian   1/12,  oc.  4.  \\inckel.  i 

previous  application  of  chloroform,  although  there  were  little  grounds  for  en- 
tertaining any  suspicions.  He  is  not  addicted  to  drugs  (Temple^'),  vocation 
(Dyer^*)  and  trauma  (Geschelin^^)  exerted  no  predisposing  influence,  and 
he  is  not  neurotic   (Fowie,^'^  Foot^').  paretic  or  epileptic   (Delthir-''). 

A  case  of  simulation  came  to  my  notice  in  June,  1900,  Miss  R,  F..  aged 
22,  from  \'an  \\'ert,  Ohio.  Consulted  in  regard  to  a  reddish  discoloration  of 
the  left  palm  and  forearm,  associated  with  shred-like  desquamation  of  two 
years'  duration.  The  case  elicited  much  local  attention  and  the  diagnosis- 
of  erysipelas  and  a  suggestion  of  ainputation  induced  the  parents  to  seek 
special  advice.  Red  chromidrosis  or  simulation  promptly  suggested  itself, 
and  a  two  weeks'  stay  in  the  hospital  with  a  plaster-of-paris  bandage  cleared 
up  the  condition  and  confirmed  the  latter  diagnosis.  A  confes.sion  from  the 
hysterical  young  woman  then  revealed  that  she  had  been  in  the  habit  of 

Page   ir.S 


M.  L.  HnlDINGSFELD 


applying  crude  carbolic  acid  locally  and  tinting  the  member  with  artificial 
rose  petals  dipped  in  water. 

I  have  been  unable  to  carry  out  any  prolonged  line  of  investigation  in 
regard  to  treatement.  It  is  somewhat  difficult  to  suggest  proper  curative 
agents,  and  the  same  futility  as  regards  treatment  no  doubt  presents  itself 
in  this  disease  as  in  chloasma,  vitiligo  and  other  pigmentary  disturbances.  I 
have  found  that  sponging  the  afi'ected  surface  locally  with  chloroform  is  an 
excellent  palliative  measure  and  prevents  the  excessive  staining  so  disagree- 
able and  annoying  to  the  patient. 

To  recapitulate,  chromidrosis  is  not,  as  its  name  implies,  an  anomaly  of 
sudoriferous  secretion.  Judging  from  the  limited  numlier  of  cases  in  the 
literature,  and  as  a  matter  of  common  observation,  it  is  an  exceedingly  rare 
aflfection  as  regards  forms  characterized  by  yellow  and  brown,  and  probablv 
black,  blue,  green  and  intermediate  shades  of  discoloration.  Red  chromidrosis 
is  an  entirely  different  and  by  no  means  an  infrequent  type  of  affection,  with 
an  extraneous  cause,  probably  some  form  of  erythro-micrococcus-tetragenus 
infection  from  individual  to  individual,  and  yielding  to  antiparasitic  reme- 
dies. In  the  light  of  this  investigation  the  pigmented  elimination,  in  the  yel 
lowish-brown  forms  at  least,  is  insoluble  in  water,  alcohol,  ether,  etc.,  is 
readily  soluble  in  chloroform,  stains  linen  indelibly,  shows  no  reaction  when 
treated  with  ordinary  reagents,  and  is  amorphous,  homogeneous  and  resinous 
in  character.  Pathologic  examination  reveals  the  sudoriferous  glands  of  the 
affected  area  to  be  normal,  sebaceous  glands  absent,  a  hyperkeratosis  around 
the  openings  of  hair  follicles  and  pigment  accumulations  near  the  hair  fol- 
licles, in  the  stratum  corneum,  lower  layers  of  the  rete,  and  the  adjacent 
cutis.  The  iiigment  is  grouped  in  cell-like  masses,  is  not  finely  granular  and 
does  not  bleach  with  hydrogen  dioxid  like  chromophores.  SiJectroscopic  ex- 
amination of  the  eliminated  pigment  reveals  no  absorption  bands  and  hence 
it  is  not  a  derivative  of  oxyhemoglobin.  In  view  of  the  pathologic  findings, 
the  absence  of  sebaceous  glands,  the  normal  condition  of  the  sudoriferous 
glands,  cases  of  so-called  chromidrosis  (  excluding  red  forms  )  are  anomalies 
of  pigmentation  and  not  glandular  secretion, 

IiIBL10GR.\PHY. 
1.     root,    Ailhui    W.:    imblin    Quart.      Review.    18(,y. 

3.  \'an   Harlingen:   Handbook-   of    Sl<in    Direa'^es.    1884,   |,.    -19. 

4.  Hyde:  Text-Boole,  1900. 

5.  li.iiis=;   .-in.l   ITai-ri.-nvav:      Text-Roolt.    1S9S. 

6.  jr.rt-vv       T,M  B.H.k.    1894. 


Stelwajon:  Tcxt-I'.oolv.  1! 
Slloemaker:  Text-Book. 
Schamberg:  Text-Book,  1 
I'ox:  .-Vtlas.  1885. 
Gottheil :  .\tlas  and  Text-: 
Jackson:  Text-Book,  1899 
Van  Harlingen:  Text-Boc 
Lesser:   I.chrbticti.   1900. 


RAXSOHOFF  MEMORIAL  VOLUME 


18.  Mracek:   Text-Book,    1899. 

19.  Bulkley:   Manual  of  Skin  Diseases,  1882. 

20.  Neumann:  Text-Book,   1877. 

21.  Labrares   et   Cabannes:    La    Medicin    Modevne,    5 
12.  Temple,   G.    H. :   Brit.    Med.   Jour.,   August,    1891. 

23.  Stott.  F.  W.  A.:  Lancet.  February.   189u. 

24.  Fowie:   Ibid. 

25.  Babesiu:  I,ancet,  1882. 

2C.  Hartzell,   M.   B.:   N.    Y.   Med.    .lour..    189.i. 

27.  Foote:   Ibid. 

28.  Labrares  et  Cabannes:   Ibid. 

29.  Hofmann:  Wien.  Med.  Woch.,  1873. 

30.  Ballowitz,   E.:  Biolog.   Centralblatt,    189,    19. 

31.  Cobn,  Moritz:  Monatsheft  f.  prak.   ncrni..    1891. 
11.  Unna:   Histopathologie  d.   Haut,   1891. 

33.  Temple:   Ibid. 

34.  Uyer,  J.:    Med.   News,    1895. 

35.  Geschelin,    J.    S. :   .Tusnor.    Medizin.    C.az..    1894. 

36.  Fowie:   Ibid. 

37.  Foote:      Ibid. 

38.  Delthil:   France  Med.,   1877. 


BRAIN   DECOMPRESSION  OPERATIONS.* 

By  H.  H.  HiNEs,  M.  D. 

Cincinnati 

To  me  it  does  not  seem  justitiahle  at  tlie  present  time,  that  a  jsatient  with 
persistent  headache,  vomiting  not  associated  with  the  taking  of  food,  begin- 
ning blindness,  choke  disc,  and  perhaps  s_\ mjitoms  pointing  to  ]iressure  in  one 
of  the  various  l)rain  areas,  should  be  abandoned  to  his  unha])]iy  fate  because 
his  physician  is  unable  to  determine  the  exact  location  and  nature  of  the 
initial  trouble. 

It  should  be  written  in  large  letters  that  brain  tumors,  abscesses,  cysts 
and  infective  granulomata.  of  the  central  nervous  system,  never  were  and 
never  will  be  cases  for  medical  treatment.  The  only  hope  of  preventing 
blindness,  ameliorating  the  other  pressure  symptoms  or  permanently  curing 
these  patients  lies  in  early  decompression,  relief  of  pressure,  and,  if  pos- 
sible, dealing  radically  with  the  lesion. 

Much  valuable  time  has  undoubtedly  been  lost  by  following  the  advice  of 
numerous  authorities,  to  subject  all  cases  ])resenting  symptoms  of  intra- 
cranial pressure  to  anti-syphilitic  treatment.  It  is  highly  improbable  tliat 
any  cases  of  gumma  sufficiently  large  to  produce  pressure  syuiptoms  have 
ever  been  benefited  by  the  mercurial-iodide  or  the  later  day  fad  arsenical 
therapeusis.    Gumma  of  the  brain  should  be  treated  as  any  other  tumor. 

It  is  intended  to  include  in  the  scope  of  this  paper  a  brief  discussion  of 
cerebral,  cerebellar  and  sellar  decompression  operations,  first,  as  a  purely 
palliative  measure,  and  second,  as  a  step  in  the  radical  removal  of  tumors, 
evacuation  of  cysts,  abscesses,  etc.  The  minute  technique  of  these  opera- 
tions will  not  be  presented,  as  they  can  be  found  in  ever)-  modern  text-book 
on  operative  surgery. 

The  technique  of  brain  operations,  representing  the  highest  type  of 
surgery,  has  shown  marvelous  progress  in  the  past  few  years.  The  question 
of  early  and  accurate  localization  has  received  much  attention,  and  the  imme- 
diate mortality,  although  high,  is  estimated  at  about  20  per  cent.  (Rawling). 

However,  so  much  depends  on  the  nature  of  the  growth,  its  position  and 
accuracy  of  localization,  and  the  personal  equation  (experience,  skill  and 
judgment  of  the  operator)  that  it  is  impossible  to  make  a  definite  statement 
as  to  the  risk  of  life  in  brain  operations.  A  recent  writer  on  the  subject 
declares  that  "the  great  secret  in  operating  on  a  brain  tumor  lies  in  knowing 
when  to  terminate  the  attempt  at  removal  of  the  tumor  and  when  to  rest 
content  with  a  pure  decompression"  (Rawling). 

There  are  two  methods  of  opening  the  skull — (a)  trephining  where  a 
button  of  bone  is  removed,  the  opening  being  subsequently  enlarged  by 
means  of  a  rongeur  forceps;  and  (b)  craniotomy,  or  the  trap-door  method  in 


RAXSOHOFF  MEMORIAL  VOLUME 


which  a  bony  flap  with  the  overlying  soft  parts  are  raised  in  one  piece.  The 
former  ]3rocediire  is  the  one  of  choice  when  a  ])alliative  decompression  is 
indicated 

CEREBELLAR    DECOMPRESSION    AXD    EXPLORATION". 
The  indications  for  cerebellar  decompression  are  chiefly  to  relieve  pres- 
sure where  tumors  are  present  in  the  lobes,  vermis,  or  cerebello-jjontine 
angle,  to  evacute  abscesses,  remove  cysts,  and  to  drain  out  blood  and  remove 
clots  in  some  cases  of  fracture  of  the  posterior  fossa. 

PREPARATIOX  OF  THE  PATIEXT. 

The  patient  is  prepared  as  for  any  major  o]ieration.  The  entire  scalp 
should  be  shaved  and  sterilization  of  the  skin  may  be  secured  1)\-  either  the 
bichloride  of  mercury  or  iodine  method.  The  use  of  urotropin  internally  for 
twenty-four  hours  or,  when  feasible,  for  several  days  before  operation,  is 
recommended.  This  drug  has  been  recovered  from  the  cerebro-spinal  fluid 
when  given  internally  and  is  supposed  to  have  antisejjtic  properties.  \"ery 
rigid  a.sepsis  is  desirable  throughout  the  operation. 

The  choice  of  an  anesthetic  is  worthy  of  some  consideration.  Some 
surgeons  jirefer  chloroform  in  brain  oj^erations  as  it  lowers  the  bluod  ]ires- 
sure  and  produces  less  congestion  in  the  vessels.  However,  as  the  lowering 
of  the  blood  pressure  may  be  a  source  of  danger  and  as  there  is  some  risk 
of  paralysis  of  the  respiratory  center,  oxygen  may  be  combined  with  chloro- 
form to  advantage.  \\t  have  u.sed  ether  or  the  gas-oxygen-elher  sequence 
in  our  operations  with  complete  satisfaction. 

The  semi-reclining  position  in  cerebral  and  the  semi-prone  in  cerebellar 
operations  is  recommended. 

The  shock  associated  with  brain  operations  is  greater  than  with  any 
other  surgical  procedure  and  all  precautions  should  be  taken  to  prevent  its 
occurrence.  The  room  must  be  warm,  the  table  should  be  heated,  and  the 
patient  protected  by  warmed  blankets.  Undue  handling  of  the  brain  should 
be  avoided  and  hemorrhage  reduced  to  a  minimum.  Horsley  uses  a  con- 
stant stream  of  warm  saline  solution  which  is  allowed  to  flow  over  the  brain 
during  the  entire  time  it  is  exposed. 

Hemorrhage  from  the  scalp  may  be  controlled  by  a  rubber  tourniquet 
passed  around  the  head,  by  temporary  ligation  of  the  chief  vessels  in  the 
neck  (Crile).  or  by  the  passage  of  sutures  through  the  base  of  the  flap 
(Kradel).  Bleeding  from  the  bone  can  be  controlled  by  plugging  with  bone 
chips,  wooden  or  ivory  pegs,  the  use  of  Horsley 's  bone  wax,  or  sterilized 
chewing  gum  (Freeman).  Injured  dural  vessels  should  be  ligated  or  encir- 
cled with  fine  wire  clips.  Bits  of  nuiscle  applied  to  bleeding  points  may  also 
be  used. 

For  cerebellar  exposures  the  horse-shoe  shajied  or  cross-bow  incision 
give  the  best  flaps.  The  curved  portion  of  the  incision  l)eing  carried  a  little 
ratic  r,2 


//.  //.  MINES 


above  the  superior  curved  line  of  the  occiput.  A  bone  flap  is  seldom  em- 
ployed owing  to  the  difficulty  of  raising  the  bone  without  injury  to  the  adja- 
cent sinuses;  furthermore,  a  hernia  is  not  apt  to  occur  in  this  location 
because  of  the  support  of  the  cervical  muscles  after  they  are  sutured. 

Pioth  bosses  and  the  median  ridge  of  the  occijjital  bone  should  be  re- 
moved. The  amount  of  tension-relief  obtained  from  a  unilateral  decom- 
pression is  not  sufficient  to  be  of  much  value.  The  two  lobes  can  be  better 
compared  as  to  tension,  bulging,  color,  etc.,  and  the  cerebello-pontine  angle 
can  be  better  exposed  by  displacing  the  lobes  to  one  or  the  other  side  in  a 
bilateral  decompression.  Absence  of  pulsation,  bulging,  discoloration,  in- 
creased firmness  or  tension  on  jialpation  are  suggestive  of  tumor,  cyst,  or 
abscess. 

Most  cases  are  treated  to  best  ad\antage  by  the  two-stage  operation — the 
second  stage  being  performed  from  ten  to  twelve  days  later,  the  wound  in 
the  soft  parts  being  entirely  closed  at  the  end  of  the  first  stage. 

Defects  in  the  dura  may  be  remedied  by  transplantation  of  a  layer  of 
e])icraniuni  or  of  the  fascia  lata. 

CEREBRAL   I-)EC0.\1PRESSI(.)X. 

As  a  palliative  measure  and  in  the  treatment  of  hemorrhage  associated 
with  fractures  at  the  base,  the  sub-temporal  operation  of  Gushing  is  in  most 
favor.  The  principal  advantage  of  this  procedure  is  that  hernia  rarely 
develops,  the  temporal  muscles  and  fascia  giving  sufficient  suj^port  to  prevent 
protrusion  of  the  brain. 

Hudson  recommends  W  or  M  shaped  Ijone  sections,  also  traji-door  bony 
flaps  fixed  in  place  by  silver  wire  sutures  to  limit  the  amount  of  outward 
displacement  of  the  flaps. 

The  skull  may  be  opened  at  any  point  over  the  cerebrum,  but  if  the  intra- 
cerebral pressure  is  not  relieved  by  evacuation  of  an  abscess  or  cyst,  or  the 
removal  of  a  tumor,  etc..  hernia  of  the  brain  is  apt  to  occur  and  will  prove 
troublesome. 

The  two-stage  operation  here,  as  in  the  cerebellum,  has  much  to  com- 
mend it 

SELL-AR  DECOMPRESSION. 

Gushing,  in  his  recent  work  on  diseases  of  the  ])ituitary  body,  refers  to 
the  transnaso-sphenoidal  removal  of  the  flour  of  the  sella  turcica  which  h;is 
proven  of  value  in  growths  and  enlargements  of  the  hypophysis.  It  allows 
of  the  extrusion  or  downward  growth  of  the  tumor  mass  and  the  consequent 
decrease  in  pressure  upon  the  adjacent  important  structures.  The  proced- 
ure is  not  of  value  in  infundibular  or  supra-hypophyseal  conditions. 

The  after  treatment,  briefly  summed  up,  is  absolute  rest  and  c(uiet  in  a 
semi-darkened  rooni,  concentrated  diet  (mostly  fluids)  ;  the  use  of  urotropin 
internally,  local  applicalic.ns  for  relief  of  pain.  Early  remo\al  of  drain 
(if  used)  and  strict  asejjsis. 

Pauc  n:i 


R.L\S()in>Ff  MEMORIAL  rOLUME 


In  conclusion,  we  wish  to  make  a  plea  for  the  early  recognition  and 
prompt  surgical  treatment  of  the  cases  of  increased  intracranial  pressure, 
which,  if  taken  in  time,  may  occasionally  be  entirely  cured  or  at  least  their 
headaches  and  vomiting  may  be  arrested,  their  vision  saved,  often  a  perverted 
mental  condition  cleared  up,  and  their  last  days  prolonged  and  spent  in  com- 
]>arative  comfort.  We  have  no  doubt  that  there  have  been  patients  in  some 
of  our  institutions  for  the  care  of  mental  diseases  that  should  ha\e  had  the 
services  of  a  surgeon. 

One  of  the  large  continental  clinics  makes  a  report  of  100  brain  cases  that 
were  operated  upon.  These  are  divisable  into  groups.  There  were  43  cases 
of  suspected  cerebral  tumor,  in  32  of  which  the  diagnosis  was  correct.  For 
cerebellar  growth  there  were  22  operations,  11  of  which  confirmed  the  diag 
nosis.  The  remainder  consisted  of  pontine  tumors  (12  cases),  pituitary 
tumors  (13  cases),  decompression  operations  (10  cases).  The  iiroportion 
of  incorrect  to  correct  diagnosis  in  cerebral  (1  in  4).  and  in  cerebellar  tumors 
( 1  in  2)  is  very  instructive.  Of  the  32  cases  where  a  tumor  of  the  cerebrum 
was  found,  9  died  of  operation,  and  12  were  alive  at  periods  \arying  from 
live  years  to  four  months. 

Of  11  cases  of  cerebellar  tumor,  five  died  of  operation,  but  only  one 
liatient  was  alive  at  the  end  of  two  years.  Of  the  12  i)online  tumors  only 
four  survived  the  operation  and  these  were  alive  for  periods  from  two  and 
one-half  to  one  year  afterward.     (Von  Eiselberg's  Clinic.) 

Due  credit  has  been  given  for  quotations  from  the  literature. 


HOSPITALS— HISTORY   OF  THEIR  DEVELOPMENT.* 
By  Christian  R.  Holmks,  M.  D.,  F.  A.  C.  S. 


Tlie  origin  of  hospital  goes  back  so  far  into  the  dim  past  that  no  data  is 
available  to  indicate  when  they  were  first  established ;  but  history  tells  us 
that  in  the  eleventh  century  B.  C.  there  was  a  college  of  physicians  in  Egypt 
in  receipt  of  public  pay,  and  regulated  by  law  as  to  the  nature  and  extent 
of  their  practice.  This  college  belonged  to  the  sacerdotal  caste,  and  women 
were  also  permitted  to  practice  medicine  there.  According  to  Pliny,  as  the 
physicians  were  paid  officers  of  the  State,  they  were  required  to  treat  the 
poor  gratuitously.  These  physicians  were  not,  however,  likely  to  attend  the 
sick  in  their  own  homes,  or  at  their  private  consulting-rooms,  except  in 
extreme  cases;  and  so  it  is  presumed  that,  as  at  Athens,  so  in  Egypt,  there 
were  official  houses  to  which  the  poor  went  at  certain  times,  and  which  cor- 
respond to  the  out-patient  departments  of  our  hospitals,  or,  better  still,  to 
our  dispensaries.  It  is  further  on  record  that  Egyptian  physicians,  though 
paid  by  the  State,  were  allowed  to  receive  fees  from  private  patients. 

At  Athens  there  were,  in  the  fifth  century  B.  C,  physicians  elected  and 
paid  by  the  citizens ;  also,  according  to  Pindarus,  dispensaries  in  which  the 
physicians  received  their  patients ;  and  there  were  at  least  two  hosiiitals 
attached  to  the  Temple  of  .Tlsculapius.  In  the  time  of  Plato  some  of  the 
Athenian  physicians  were  elected  by  the  people  and  paid  by  the  treasury. 
Socrates  speaks  of  one  desiring  to  obtain  a  medical  appointment  from  the 
government,  and  there  was  a  technical  term  applied  especially  to  physicians 
who  had  a  public  salary.  These  State  physicians,  after  election,  appear  to 
have  appointed  slave-doctors  under  them  to  attend  the  poor,  while  they 
themselves  attended  to  the  rich,  and.  either  by  their  own  eloquence  or  by 
that  of  some  friendly  rhetorician,  persuaded  the  patients  to  drink  the  medi- 
cine, or  submit  to  the  knife  or  the  hot  iron.  The  slave-doctors,  on  the  other 
hand,  had  no  such  scruples,  but  ran  about  from  one  patient  to  another,  and 
dosed  them  as  they  thought  proper,  or  "waited  for  them  in  their  dispens- 
aries." This  passage  shows  that  there  were  at  Athens,  in  the  fifth  cen- 
tury B.  C,  dispensaries  to  which  the  sick  poor  repaired  for  treatment  of  their 
diseases  by  the  slave-doctors,  who  were  appointed  and  paid  by  the  State 
physicians  to  look  after  ailments  of  the  poor.  These  dispensaries  varied  in 
number,  according  to  the  prevalence  of  diseases. 

In  Hippocrates  himself — "The  Father  of  Medicine,"  as  he  has  been 
called — we  find  the  spirit  which  characterises  our  modern  charity  hospitals. 
In  the  oath  by  which  he  bound  himself  to  his  profession  there  is  the  declara- 
tion that  he  would  all  his  life  visit  the  sick  and  give  them  his  advice  gratis — 


RAXSOHOFF  MEMORIAL  VOLUME 


a  resolution  which  would  certainly  bring  him  a  large  practice,  resembling  tlie 
out-patient  department  of  a  hospital :  and,  indeed.  Pindarus  tells  us  of 
houses  in  Athens,  officially  chosen,  where  the  sick  poor  repaired  at  fixed 
times — in  fact,  dispensaries.  \\'e  meet.  also,  with  one  allusion  to  a  ho>pital. 
This  institution  is  mentioned  by  the  comic  poet.  Crates,  whu  lived  about  the 
middle  of  the  fourth  century  B.  C. 

That  medical  science  had  attained  a  high  degree  of  iH'rfection  in  Egyp; 
may  be  inferred  from  the  fact  that  there  were  specialists  in  different  branches 
of  the  art.  and  each  physician  was  allowed  to  practice  only  his  own  branch. 
The  Egyptians  had  oculists  and  dentists,  the  latter  of  whom  were  skillful 
enough  to  be  able  to  stop  teeth  with  gold,  as  the  Theban  mummies  show. 
Moreover,  one  of  their  kings — Athothis.  son  and  successor  to  Menes.  the 
first  king  of  Egypt — wrote  a  treatise  on  anatomy.  At  what  period  medical 
science  in  Egypt  emancipated  itself  from  superstition  is  uncertain;  but  a 
medical  papyrus,  now  at  Berlin,  which  dates  from  the  fourteenth  century 
r>.  C,  contains  a  copy  of  a  treatise  on  inflammation,  which,  the  papyrus 
states,  was  found  written  in  "ancient  writing"  rolled  Uj)  in  a  cotter,  under 
the  feet  of  Anubis,  in  the  town  of  Sokheni,  in  the  time  of  his  sacred  majesty, 
Thot  the  Righteous.  After  the  death  of  this  monarch  it  was  handed  to  King 
Snat,  on  account  of  its  importance.  It  was  then  copied  and  restored  to  its 
place  under  the  feet  of  the  statue,  and  sealed  up  by  the  sacred  scribe  ;uid 
wise  chief  of  the  physicians. 

In  India.  King  Asoka.  who  reigned  in  the  third  century  11.  C  ,  published 
an  edict  commanding  the  establishment  of  hospitals  throughout  his  domains. 
Monarchs  and  their  advisers  seldom  invent — they  systematize;  and  it  is 
more  than  probable  that  King  Asoka's  edict  was  meant  to  improve  rather 
than  to  initiate  a  hospital  system.  The  king's  edicts  are  still  e.xlant ;  for 
they  are  engraven  in  the  living  rock  in  Gujerat.  not  far  from  the  town  of 
Surat ;  and  there  is  also  a  legend  that,  grieve<l  at  seeing  how  often  people 
died  from  diseases  that  could  easily  be  cured,  Asoka  established  dispensaries 
at  the  four  gates  of  his  royal  city  of  Patna.  The  royal  fashion  spread,  and 
in  the  year  399  A.  D..  six  hundred  years  after  Asoka  died,  a  Chinese  trav- 
eler. Fa-Hian,  visited  India,  and  found  there  hospitals,  which  in  all  essentials 
resembled  our  modern  institutions.  He  says  in  his  Travels :  "The  nob'es 
and  landowners  of  this  country  ha\e  founded  hosi)itals  in  the  city,  to  which, 
the  poor  of  all  countries,  the  destitute,  the  cri])])les.  the  diseased,  may  repair 
for  shelter.  They  receive  every  kind  of  requisite  help  gratuitously.  Physi- 
cians inspect  their  diseases,  and  according  to  their  cases,  order  them  food 
and  drink,  decoctions  or  medicines,  everything,  in  fact,  that  may  contribute 
to  their  ease.    When  cured  they  depart  at  their  own  convenience." 

Of  .Asoka's  hospitals,  one.  and  one  only,  existed  at  the  commencement 
of  the  j)rescnt  centurw  Hospitals  for  the  pucir  .nnd  sick  b:id  entirely  dis- 
appeared at  the  time  of  llu-  I'.ritish  occu|)ati(in  dl  liuli.i.  The  last  remaining 
of  -Asoka's  was.  strange  to  say.  dexoted  to  the  treatment  of  ;ininials.  It 
Paije  r.ii 


CHRISTIAN  R.  HOLMES 


covered  twenty-five  acres,  and  was  divided  into  proper  wards  and  courts 
for  the  accommodation  of  the  patients.  When  an  animal  was  sick  or  injured, 
its  master  had  only  to  hring  it  to  the  hospital,  where  it  was  recei\ed  and 
tended  without  regard  to  the  caste  of  its  owner;  and,  where,  if  necessarv, 
it  found  an  asylum  in  old  age.  So  careful  were  the  doctors  there  of  the 
patients,  that  a  traveler  reports  their  purchasing  bread  and  milk  for  two 
animals  which  could  not  crop  grass. 

In  Rome,  which  so  largely  imitated  the  civilization  of  Greece,  we  find 
the  Athenian  custom  of  having  public  physicians  in  every  city.  The  number 
of  these  in  each  center  was  proportionate  to  the  number  of  the  inhabitants, 
and  they  received  salaries  from  the  public  treasury. 

It  should  be  noted,  also,  that  the  luxurious  public  baths  erected  under  the 
Roman  Empire  were  primarily  intended  for  the  poor.  They  were  free  to 
all.  The  subsequent  abuse  of  them  by  the  rich  and  pleasure-loving  belonged 
to  the  general  corruption  of  society  which  thwarted  and  misapplied  the 
original  charity. 

The  Temple  of  .lisculapius,  situated  on  an  ishuifl  in  the  Tiber,  was 
according  to  the  practice  of  classic  times,  also  a  hospital  and  one  to  which 
certain  privileges  attached ;  for  the  Emperor  Claudius  promulgated  a  law 
which  ordained  that  slaves  whose  masters  abandoned  them  on  the  island 
of  ^sculapius  should  be  held  free  if  they  recovered  from  their  illness. 

As  the  Christian  religion  assumed  importance  and  became  paramount 
in  the  State  the  hospital  system  extended  throughout  the  Roman  Empire  on 
lines  at  once  more  methodical  and  more  distinctly  charitable  than  before. 
Hospitals  for  the  sick  early  became  an  integral  part  of  society  institutions. 
W'e  learn  that,  about  the  )ear  258  A.  D.,  Laurentius,  chief  of  the  deacons, 
assembled  a  great  number  of  poor  and  sick,  who  were  supported  by  the  alms 
of  the  church.  W'e  cannot  be  sure,  however,  that  this  assemblage  enjoyed 
medical  treatment  as  well  as  alms ;  but  it  is  a  fact  that,  in  the  year  380  A.  D., 
a  regular  hospital  was  founded  by  Fabiola.  a  Roman  matron  of  distinguished 
piety.  She  instituted,  St.  Jerome  informs  us,  a  nosocomium,  which  he  de- 
fines as  "a  house  in  the  country  for  the  reception  of  those  unhappily  sick  and 
infirm  persons  who  were  before  scattered  among  the  places  of  public  resort  ; 
where  they  would  be  furnished  in  a  regular  manner  with  nourishment  and 
those  medicines  of  which  they  might  stand  in  need."  This  establishment  was 
situated  at  some  distance  from  the  city,  in  a  healthy  jjart  of  the  country. 
The  fame  of  this  institution  spread,  we  are  told,  throughout  the  Roman 
Empire,  "from  the  Egytpians  and  Parthians  to  the  cities  of  Britain." 

Another  hospital  was  built  by  St.  Basil,  outside  the  walls  of  Caesarea 
and  Cappadocia,  founded,  probably,  on  the  site  of  an  earlier  hospital.  This 
edifice  was  so  large  that  St.  Gregory  Nazianzen  says  it  "rose  to  view  like  a 
second  cily,  the  abode  of  charity,  the  treasury  into  which  the  rich  poured 
of  their  wealth  and  the  \)oot  of  their  po\frly.  Here,  disease  was  inves- 
tigated and  sympathy  proved." 

Pas/c  m 


RAXSOHOFF  MEMORIAL  l\)LUME 

When  St.  John  Chrysostom  went  to  Constantinople,  he  found  there  at 
least  one  hospital,  and  built  many  others  on  the  plan  of  the  Basileas  and 
Caesarea.  There  must  have  been  a  considerable  number  of  hospitals  in 
Alexandria  about  this  time,  for  a  law  of  the  Emperor  Honorius  mentions  no 
fewer  than  six  hundred  nurses,  who  were  placed  at  the  disposal  of  the  bishop 
for  the  purpose  of  nursing  the  sick.  Three  nurses  bore  the  name  of  para- 
bolani,  which  originally  signified  nurses  in  infectious  diseases,  the  title  signi- 
fying those  who  cast  themselves  into  danger  of  death  with  a  divine  reck- 
lessness. 

Among  the  Romans,  the  first  military  hospital  we  hear  of  was  estab- 
lished in  the  time  of  Hadrian.  It  was  in  connection  with  the  army  that  hos- 
pitals which  must  certainly  be  regarded  as  such  sprang  up.  In  the  year 
90  A.  D.,  Agathines,  a  Lacedemonian,  opened  a  school  of  medicine  in  the 
imperial  city,  and  about  the  same  time  institutions  termed  valetudinaria 
and  veterinaria  were  in  active  operation  for  the  treatment  of  infirm  soldiers 
and  their  horses.  They  were  attached  to  the  legionary  camp  during  war 
as  an  indispensable  feature,  and  replaced  the  tent,  where  up  till  then  the 
sick  or  wounded  warrior  had  been  brought.  If  the  army  changed  its  quar- 
ters the  patient  was  transported  to.  and  laid  in,  some  neighboring  cottage. 
Treatment  appears  to  have  been  principally  surgical  in  character.  These 
valetudinaria  were  attached  to  the  winter  quarters  of  the  soldiery,  and  praise 
was  given  to  those  generals  who  visited  the  sick  and  wounded.  The  Emperor 
Tiberius,  both  before  and  after  his  accession  to  the  purple,  was  especially 
solicitous  for  his  soldiers,  and  added  to  their  conveniences  ambulances  for 
their  easier  transport,  and  baths  for  their  comfort. 

Military  hospitals  existed  not  only  in  the  Eastern  Hemisphere,  but 
among  the  ancient  Mexicans,  whose  strange  and  elaborate  civilization 
Europeans  have  as  yet  done  more  to  destroy  than  to  replace.  They  had 
hospitals  in  their  principal  cities  "for  the  cure  of  the  sick,  and  for  the  per- 
manent refuge  of  disabled  soldiers."  Over  these  hospitals  were  placed 
surgeons,  who,  says  a  grumbling  chronicler — Torquemada — "were  so  far 
better  than  those  of  Europe  that  they  did  not  protract  the  cure  in  order  to 
increase  the  pay."  (Prescott,  History  of  the  Conquest  of  Mexico,  book  1, 
ch.  2.)  Bancroft,  in  his  "Native  Races  of  the  Pacific  States  of  North 
.America,  affirms  (vol.  ii.  p.  596  et  seq.)  that  in  all  the  larger  Mexican  cities 
there  were  hospitals  amply  endowed,  and  attended  by  experienced  physicians, 
surgeons  and  nurses ;  that  the  ^Mexicans  had  studied  and  practiced  medicine 
from  ancient  times ;  that  they  possessed  botanic  gardens,  and  suitable  places 
and  arrangements  for  dissection:  that  all  their  midwives  were  women;  and 
that  female  doctors  were  common  among  them. 

Medical  women  were  to  be  found  elsewhere,  also,  in  ancient  days — even 
in  the  comparatively  unknown  kingdom  of  Siam.  Here  still  exists  the  oldest 
hospital  for  women  of  which  we  have  any  knowledge.  It  is  in  Bangkok,  the 
capital  of  Siam.     The  inhabitants  of  this  ancient  and  jjopulous  city  live,  for 


CHRISTIAN  R.  HOLMES 


the  most  part,  in  houses  built  upon  rafts  floating  on  the  river  Meinam ;  and 
all  the  physicians  of  the  Court,  both  male  and  female,  are  compelled  to  give 
their  services  gratuitously  to  each  of  the  hosjjitals  that  may  require  them. 
(  Hamilton  Hindostan,  Vol.  I.) 

From  the  collection  of  poems  entitled  "Shah  Namah,"  which  deals  with 
the  ancient  history  of  Persia,  we  learn  that  the  fire-worshippers  had  hos- 
pitals from  the  earliest  times — an  evidence  of  humanity  which  we  cannot 
think  strange  in  the  followers  of  Zoroaster.  The  traditional  stories  of  the 
tenderness  of  Buddha  also  make  it  natural  that  his  followers  should,  as  we 
know  they  have  done,  establish  hospitals ;  and  we  read  in  Tumour's  transla- 
tion of  the  books  of  the  southern  Buddhists  that  "Buddha  appointed  a 
l)hysician  for  every  ten  villages  on  the  highroad,  and  built  asylums  for  the 
crippled,  the  deformed,  and  the  destitute.  His  son  Upatisso  built  hospitals 
for  cripples,  for  women,  and  for  the  blind  and  diseased ;  and  Dhatusenrl 
built  hospitals  for  the  crippled  and  for  the  sick." 

These  facts  indicate  that  hospitals,  though  now  almost  identified  with 
the  Christian  religion,  are  the  outcome  of  the  innate  tenderness  that  marks 
all  noble  souls,  in  whatever  land  they  dwell  and  in  whatever  creed  they  are 
conceived.  But,  before  proceeding  to  the  consideration  of  the  hospitals  of 
the  medieval  times,  it  may  be  worth  while  to  mention  hospitals  that  were 
built  for  no  other  reason  than  enmity  to  Christ.  The  Emperor  Julian  (The 
Apostate)  perceiving  that,  as  he  i)uts  il,  "these  impious  Galileans  give  them- 
selves to  this  kind  of  humanity,"  ordered  Arcacius  to  "establish  abundance 
of  hospitals  in  every  city,  that  our  kindness  may  be  enjoyed  by  strangers, 
not  only  by  our  own  people,  but  by  those  who  are  in  need."  Thus  he  thought 
to  emulate  and  surpass  the  Christians.  ^ 

Soon  after  the  commencement  of  the  Christian  era.  specialism  pre\ailed 
to  an  inordinate  extent,  and  oculists,  dentists,  aurists,  hydropists.  and  even 
fistulists  were  numerous,  as  well  as  special  pharmacists  for  herbal  remedies, 
ointments,  eye-washes,  and  the  like.  Many  women  practiced  in  those  times, 
and  lady  obstetricians  were  in  high  favor,  .\ccording  to  Haeser,  open 
surgeries  were  the  rule,  though  they  varied  much  as  to  character,  price  and 
respectability.  These  "tabernse  medicse"  led  directly  to  the  establishment  of 
hospitals,  as  it  was  found  desirable  in  certain  cases  to  have  the  patient  under 
constant  observation,  and,  so,  rooms  were  set  aside  in  connection  with  these 
establishments  for  the  reception  of  in-patients.  Galen  and  Plautis  give  par- 
ticulars of  the  tabernae  medicse  or  iatria,  which  were  erected  by  many  towns 
at  their  own  cost.  They  were  frequently  large  buildings,  so  constructed  as 
to  admit  abundance  of  air,  and  were  provided  with  surgical  instruments  and 
medical  appliances  of  all  kinds. 

Of  hospitals  which  were  not  the  direct  off-shoots  of  monasteries,  the 
olde.st,  so  far  as  we  can  tell,  is  still  great  and  flourishing — the  Hotel  Dieu, 
"God's  Hostelry,"  in  Paris,  founded  by  St.  Landry,  Bishop  of  Paris,  at  his 
own  cost  in  the  year  of  600  A.  D.    This  was,  in  its  original  form,  more  than 


RAXSOlIUl'l'  MI-MUKIJL  VULUMll 


simply  a  place  where  the  sick  were  tended.  It  was  a  charitable  organization 
which  embraced  every  form  of  aid  to  the  ixKir  and  need}'.  The  functions  of 
the  inn.  the  workhouse,  and  the  asyhnn.  as  well  as  those  of  the  infirmary 
were  concentrated  in  the  Hotel  Dieu. 

( )ne  of  the  oldest  English  hospitals — at  least  the  one  whose  reliable  rec- 
ords bear  the  earliest  date — is  St.  Bartholomew's  Hospital.  It  was  founded 
between  1123  and  1133  by  Rahere,  the  jester  of  King  Henry  I.  who,  like  the 
Chicot  of  history  and  the  Jaques  of  poetry,  grew  tired  of  fooling  and  joined 
a  religious  order,  and  obtained  from  the  king,  his  old  master,  who  still  cher- 
ished an  affection  for  his  faithless  jester,  the  grant  of  an  empty  space  of 
ground  in  the  west  suburbs  of  London,  called  Smithfield.  There  he  built  a 
priory,  and  on  the  south  side  of  this  he  erected  a  hospital.  The  original 
"Bart's"  though  on  a  smaller  scale  than  the  present,  was  meant  to  fulfill  a 
wider  scope.  It  was  meant  not  only  for  "poor  diseased  persons  till  they  got 
well."  but  for  reception  of  obstetric  cases ;  and  it  also  provided  for  the 
maintenance  of  all  children  in  the  hospital  until  they  reached  the  age  of 
seven,  if  their  mothers  had  died  there. 

St.  Bartholomew's  Hospital  presented  from  the  first  exceptional  oppor- 
tunities for  the  study  of  surgery.  The  original  name  of  Smithfield  was 
"Smoothfield,"  and  its  green  meadow  was  a  favorite  scene  of  jousts  and 
tournaments,  A  tradition  of  its  old  fame,  before  first  martyrs  and  then 
cattle  became  connected  with  it,  survives  in  the  name  of  "Giltspur  Street," 
which  still  indicates  the  road  by  which  the  gaily-caparisoned  knights  rode 
to  those  "gentle  and  joyous"  sports  which  so  often  ended  in  wounds  and 
death.  These  wounded  knights  would,  not  improbably,  be  taken  to  St. 
Bartholomew's  Hospital,  where  the  brethren — the  house-surgeons  of  those 
days — could  apply  oil  and  wine,  and,  where  necessary,  the  actual  cautery, 
or  the  boiling  pitch,  with  all  the  skill  and  tenderness  of  which  they  were 
masters. 

King  John,  of  inglorious  memory,  deserves  a  kindly  thought  in  connection 
with  St.  Bartholomew's  Hospital  for  a  charter  confirming  the  annexation  of 
the  hospital  to  the  priory,  and  threatening  with  confiscation  of  goods  any  one 
who  should  interfere  with  its  vested  interests.  The  individual  who  should 
separate  the  two  branches  arose  some  centuries  later  in  the  person  of  Henry 
VIII.,  who  had  no  cause  to  fear  King  John's  threat.  That  threat  merely 
ordained  that  the  goods  of  the  wrong-doer  should  be  confiscated  to  the  king, 
so  King  Henry  confiscated  his  own  goods  ;ind  ihe  church's  also  to 
himself.  This  was  naturall\-  a  scrimts  niaittT.  not  only  for  the  master, 
brethren  and  sisters  of  the  hnspilal.  Im!  ior  the  poor  and  the  infirm 
whom  they  h;i(l  tended  there;  and  on  a  |ictilion  being  laid  before  him 
by  the  ni,-iyor.  aldcrnu-n  ;ind  connnonalty  of  the  city  of  I,on<ion,  in 
153<S  His  Majesty  was  ])!eased  to  permit  the  m;iyor  to  ha\e  the  govern- 
ment of  St.  P.artholoniew's  Hosjiilal ;  and,  further,  in  tlic  thirty-sixth 
year  of  his  reign  (1554)  King  Henry  re-established  the  ho.^pital  on  a  .secular 

I'auc  imi 


CHRISTIAN  R.  HOLMES 


basis,  for  which  he  is  revered  as  the  second  founder.  He  appointed  as  chief 
officers  of  the  hospital  a  master,  priest,  and  four  chaplains,  the  first  to  be 
called  the  vice-master,  the  second  the  curate,  the  third  the  hospitaller,  and 
the  fourth  the  visitor  of  prisoners  in  Newgate,  which  stood  within  the  i):irish 
of  St.  Bartholomew.  Besides  these  there  was  appointed  a  matron  with 
twelve  sisters  under  her  to  attend  to  the  sick. 

What  nursing  was  in  those  days  may  be  gathered  from  the  fact  that 
these  twelve  nurses  were  ordered,  when  their  daily  work  among  their  jiatients 
was  done,  to  occupy  themselves  in  spinning,  .sewing,  mending  of  sheets  and 
shirts,  or  some  other  virtuous  exercise  such  as  they  should  be  appointed  unto. 

From  what  I  have  just  quoted,  you  will  see  that  the  eiTorts  to  relieve 
sick  and  sulTering  humanity  have  perhaps  existed  as  long  as  man  himself 
in  one  form  or  another;  that  this  phase  of  helpfulness  to  fellow  human 
beings  in  distress  has  varied  through  thousands  of  years,  dejiending  ui)on  the 
rise  and  fall  of  nations. 

However,  the  fact  remains  that  before  the  discovery  of  the  bacterial 
origin  of  disease,  about  fifty  years  ago,  especially  as  the  result  of  the  won- 
derful works  of  Louis  Pasteur,  hospitals,  while  intended  as  places  of  refuge 
and  restoration  to  health  of  the  sick,  often  became  veritable  pestholes,  as 
was  shown  by  Florence  Nightingale  in  a  table  of  statistics  showing  the  mor- 
tality percentages  in  some  of  the  jM-incipal  hospitals  of  England  during  the 
year  1861.  She  says:  "We  have  twenty-four  London  hospitals,  affording 
a  mortality  of  no  less  than  90.84  per  cent.,  very  nearly  every  bed  yielding 
a  death  in  the  course  of  the  year.  Next,  we  have  twelve  hospitals  in  large 
provincial  towns — Bristol,  Birmingham,  Liverpool,  Manchester,  etc.,  yielding 
a  date  rate  of  83.16  per  cent.  And  there  are  twenty-five  county  hospitals  in 
country  towns  the  mortality  in  which  is  no  more  than  39.41  per  cent.  Here 
we  have  at  once  a  hospital  problem  demanding  solution.  However  the  great 
differences  in  the  death  rates  may  be  explained,  it  cannot  be  denied  that  the 
most  unhealthy  hospitals  are  those  situated  within  the  vast  circuit  of  the 
metropolis ;  and  the  next  lower  death  rate  takes  place  in  hospitals  in  densely 
populated  large  manufacturing  and  commercial  towns,  and  that  bv  far  the 
most  healthy  hospitals  are  those  of  the  smaller  country  towns.  But  by  far 
the  most  remarkable  illustration  of  the  effects  produced  on  the  sick  and 
maimed  by  agglomeration  is  that  afforded  by  the  experience  of  the  Hotel 
Dieu.  at  the  latter  end  of  the  last  century,  and  before  its  reconstruction.  It 
will  be  observed  that  there  was  direct  atmospheric  communication  through 
the  entire  suite  of  wards  occupied  by  about  550  beds  on  a  single  floor.  The 
whole  hospital  contained  1200  beds.  But  the  number  of  beds  by  no  means 
represented  the  number  of  sick,  who  were  sometimes  placed  in  the  beds  as 
close  together  as  they  could  lie.  In  this  way  from  2000  to  5000,  or  even 
7000  sick  were  sometimes  in  the  hospital  at  one  time. 

"So  late  as  the  year  1788,  each  of  the  beds  in  the  Hotel  Dieu  was  intended 
to  hold  either  two  or  four  sick.    There  is  an  extremely  curious  notice  of  this 


RAN  son  OF  I-  MEMORIAL  VOLUME 


subject  in  M.  Husson's  given  in  Note  C.  From  this  it  appears  that  in  the 
sixteenth  century,  notwithstanding  tlu-  use  of  inuhiple  beds,  holding,  in  1515, 
from  eight  to  twelve  patients  each,  the  number  of  sick  so  far  exceeded  the 
bed  accommodation  that  the  beds,  in  1530,  were  occupied  by  relays  of 
patients,  and  that  forms  were  provided  on  which  the  sick  whose  turn  it  was 
to  be  out  of  bed  could  rest  in  the  meantime." 

Florence  Nightingale  anticipated  in  her  writings  sanitary  jiroblems  that 
we  are  introducing  to-day.  I  beg  to  quote  a  couple  of  passages;  '"W'here- 
ever  cubic  space  is  deficient,  ventilation  is  bad.  Cubic  space  and  ventilation 
will,  therefore,  go  hand  in  hand.  The  law  holds  good  with  regard  to  hos- 
pitals, barracks,  and  all  inhabited  places.  If  overcrowding,  or  its  concomi- 
tant, bad  ventilation,  among  healthy  people,  generates  disease,  it  does  so  to  a 
far  greater  extent  amojig  the  sick  is  hospitals.  In  civil  hospitals  the  amount 
of  cubic  space  varies  between  600  and  2000  cubic  feet  per  bed.  In  some 
military  hospitals  it  used  to  be  under  300,  and  from  700  to  800  was  consid- 
ered a  somewhat  extravagant  allowance.  The  old  army  practice  of  allotting 
only  from  600  to  800  cubic  feet  per  bed  in  hospitals  was  the  cause  why  army 
hospitals  proved  to  be  so  unhealthy.  At  Scutari,  at  one  time,  not  even  half 
the  regulation  space  was  given,  and  great  overcrowding  consequent  there- 
upon was  one  element  in  the  disastrous  result  which  followed.  Anyone  in 
the  habit  of  examining  hospitals  with  different  relative  amounts  of  cubic 
space  cannot  fail  to  have  been  struck  with  the  very  different  appearance  of 
the  sick,  and  with  the  different  state  of  the  ward  atmosphere.  Cubic  space  is 
an  essential  element  in  the  question  of  ventilation.  It  is  impossible,  with 
due  regard  to  warmth,  to  ventilate  a  ward  in  a  lirick  or  stone  hospital 
without  mechanical  means  when  the  space  ])er  bed  is  less  than  a  cer- 
tain amount.  Crowded  wards  are.  in  fact,  oft'ensive.  with  all  the 
windows  open.  Under  all  circumstances,  however,  the  progress  of  the  cases 
(in  solidly-built  hospitals)  will  betray  any  curtailment  of  space  much  below 
1,500  cubic  feet.  The  master  of  some  large  works  in  London  lately  men- 
tioned the  following  fact :  He  was  in  the  habit  of  sending  those  of  his 
workmen  who  met  with  accidents  to  two  different  metropolitan  hospitals. 
In  one  they  recovered  quickly ;  in  the  other  they  were  frequently  attacked 
with  erysipelas,  and  some  cases  were  fatal.  On  inquiry  it  appeared  that  in 
the  former  hospital  a  larger  amount  of  space  was  allowed  than  in  the  latter, 
which  is  also  so  deficient  in  external  ventilation  and  in  construction,  that 
nothing  but  artificial  ventilation  could  effectively  change  its  atmosphere. 

"It  is  even  more  important  to  have  a  sufficient  surface-area  between  the 
adjoining  and  the  opposite  beds.  Piling  space  above  the  patient  is  not  all 
that  is  wanted.  In  the  lofty  corridors  of  Scutari.  I  have  seen  two  long  rows 
of  opposite  beds  with  scarcely  three  feet  from  foot  to  foot.  Certainly  it 
cannot  be  thought  too  much,  under  any  circumstances,  to  give  eath  bed  a 
territory  to  itself  of  at  least  eight  feet  wide  by  twelve  or  thirteen  feet  long. 


CHRISTIAN  R.  HOLMES 


"The  want  of  fresh  air  may  be  detected  in  the  appearance  of  patients 
sooner  than  any  other  want.  No  care  or  luxury  will  compensate,  indeed, 
for  its  absence.  Unless  the  air  zi'ithin  the  ward  can  be  kept  as  fresh  as  it  is 
without,  the  patients  had  better  be  away.  What  must  then  be  said  when, 
as  in  some  town  situations,  the  air  without  is  not  fresh  air  at  all?  Except 
in  a  few  cases,  well  known  to  physicians,  the  danger  of  admitting  fresh  air 
directly  is  very  much  exaggerated.  Patients  in  bed  are  not  peculiarly 
inclined  to  catch  cold  (note  'catching  cold'  in  bed  follows  the  same  law  as 
'catching  cold'  when  up.  If  the  atmosphere  is  foul,  and  the  lungs  and  skin 
can  not  therefore  relieve  the  system,  then  a  draught  upon  the  patient  may 
give  him  cold.  But  this  is  the  fault  of  the  foul  air,  not  of  the  fresh.  In  the 
wooden  hospital  huts  before  Sebastopol,  with  their  pervious  walls  and  open 
ridge  ventilators,  in  which  the  patients  sometimes  said  that  they  'would  get 
less  snow  if  they  were  outside,'  such  a  thing  as  'catching  cold"  was  never 
heard  of.  The  patients  were  well  covered  with  blankets,  and  were  all  the 
better  for  the  cold  air).  In  England,  where  fuel  is  cheap,  somebody  is  indeed 
to  blame,  if  the  ward  cannot  be  kept  warm  enough,  and  if  the  patients 
cannot  have  bed  clothing  enough,  for  as  much  air  to  be  admitted  from  with- 
out as  suffices  to  keep  the  ward  fresh.  No  artificial  ventilation  will  do  this. 
.'Mthough  in  badly-constructed  hospitals,  or  in  countries  where  fuel  is  dear, 
and  the  winter  very  cold,  artificial  ventilation  may  be  necessary — it  never  can 
compensate  for  the  want  of  the  open  window.  The  ward  is  never  fresh, 
when  artificially  ventilated.  It  will  be  found  that,  till  the  windows  are 
opened,  the  air  is  close.  A  well-waged  controversy  has  lately  been  carried 
on  upon  this  very  point,  in  Paris.  Eminent  authorities  in  England  had  de- 
cried the  pavilion  system,  on  the  ground  that  the  atmosphere  of  a  certain 
Paris  pavilion  hospital  was  'detestable,'  not  because  of  the  pavilion  archi- 
tecture, but  because  of  its  artificial  ventilation  defying  the  best  pavilion 
building  to  ventilate  its  patients.  What  is  all  that  luxury  of  magnificent 
windows  for  but  to  admit  fresh  air?  To  shut  up  your  patients  tight  in  arti- 
ficially warmed  air,  is  to  bake  them  in  a  slow  oven.  Open  the  windows, 
warm  it  with  open  fires,  drain  it  properly,  and  it  will  be  one  of  the  finest 
hospitals  in  the  world.  Natural  ventilation,  or  that  by  open  windows  and 
open  fireplaces,  is  the  only  efficient  means  for  procuring  the  life-spring  of 
the  sick — fresh  air.  The  amount  of  fresh  air  required  for  ventilation  has 
been  hitherto  very  much  underrated,  because  it  has  been  assumed  that  the 
quantity  of  carbonic  acid  produced  during  respiration  was  the  chief  noxious 
gas  to  be  carried  off.  The  total  amount  of  this  gas  produced  by  an  adult  in 
twenty-four  hours  is  about  40,000  cubic  inches,  which  in  a  barrack-room,  say, 
containing  sixteen  men,  would  give  370  cubic  feet  per  diem.  Allowing 
eight  hours  for  the  night  occupation  of  each  room,  when  the  doors  and 
windows  may  be  supposed  to  be  shut,  the  product  of  carbonic  acid  would  be 
123  cubic  feet,  or  about  fifteen  and  one-half  cubic  feet  per  hour.  This  large 
quantity,  if  not  speedily  carried  away,  would  undoubtedly  be  injurious  to 

Page  IHS 


RANSOHOFI'  MEMORIAL  I'OLVME 


health,  but  there  are  other  gaseous  poisons  produced  with  the  carbonic  acid 
which  have  still  greater  power  to  injure.  Every  adult  exhales  by  the  lungs 
and  skin  forty-eight  ounces,  or  three  pints  of  water,  in  twenty-four  hours. 
Sixteen  men  in  a  room  would  therefore  exhale  in  eight  hours,  sixteen  pints 
of  water,  and  123  cubic  feet  of  carbonic  acid,  into  the  atmosphere  of  the 
room.  With  the  watery  vapor  there  is  also  exhaled  a  large  quantity  of 
organic  matter,  ready  to  enter  into  the  putrefactive  condition.  This  is  espe- 
cially the  case  during  the  hours  of  sleep,  and  as  it  is  a  vital  law  that  all 
excretions  are  injurious  to  health  if  reintroduced  into  the  system,  it  is  easy 
to  understand  how  the  breathing  of  damp  foul  air  of  this  kind,  and  the  con- 
sequent re-introduction  of  excrementitious  matter  into  the  blood  through  the 
function  of  respiration,  will  tend  to  produce  disease." 

Whatever  arguments  there  may  have  been  against  hospitals  prior  to  the 
discovery  of  the  germ  origin  of  disease  have  now  entirely  vanished  and  the 
modern  hospital,  built  according  to  the  latest  standards — fire-proof,  germ- 
proof,  located  upon  favorable  sites,  e\ery  bed  so  placed  as  to  be  bathed  in 
life-giving  sunlight  and  fresh,  pure  air,  with  modern  laboratories  containing 
the  latest  instruments  of  precision,  a  staflf  of  highly  trained  physicians  and 
nurses  and  dietitians,  the  hospital  has  come  to  not  alone  take  care  of  the 
sick  poor,  but  the  wealthy  as  well — for  no  home  can  furnish  all  the  advan- 
tages just  enumerated.  It  is  for  these  reasons  that  hospitals  of  the  type 
just  described  are  springing  up  all  over  this  country  and  Europe  witli 
marvelous  rapidity. 

In  Germany  the  number  of  hospitals  increased  from  3000  hospitals  with 
140.000  beds,  in  1,S76,  to  6300  hospitals  with  370,000  beds,  in  1900— an  in- 
crease of  250  per  cent,  in  twenty-five  years.  This  great  increase  has  caused 
many  men  and  women  to  give  special  thought  to  the  development  and  plan- 
ning of  these  iiistitutions. 

The  subject  of  hospital  construction  differs  from  every  other  kind  of 
building,  in  that  the  various  departments  of  medicine  and  sanitation  in  their 
broadest  sense  are  constantly  undergoing  progressive  changes,  because  of 
new  discoveries,  and,  as  a  result,  our  efforts  to  meet  and  anticipate  these 
new  conditions  In  a  modern  hos])ital  reejuire  uiuisual  care  and  foresiglit  in 
planning. 

In  many  instances,  when  a  nuniicipality,  or  organization,  or  a  wealthy 
philanthropist,  determines  to  build  a  hosjiital,  a  board  of  directors  or  com- 
missioners is  created  to  carry  out  the  ])roject.  The  men  placed  in  charge 
often  have  not  the  slightest  knowledge  of  the  needs  of  a  hospital,  be  they 
laymen  or  physicians ;  for  it  is  a  fact  that  many  of  our  most  brilliant  physi- 
cians ha\e  never  given  the  subject  of  hospital  construction  any  thought — 
and,  as  the  subject  of  hospital  construction  is  really  a  special  department, 
their  lack  of  knowledge  is  not  so  much  to  be  wondered  at — but  I  wish  to  call 
attention  to  this  fact,  because  the  general  jjublic  take  it  for  granted  that 
every  doctor  must  be  an  authority  on  anything  pertaining  to  hospitals,  and 


CHRISTIAN  R.  HOLMES 


hence  are  often  misled  by  off-hand  opinions  given  by  members  of  the  profes- 
tiion  who  are  not  qualified  to  speak. 

The  architect  is  often  selected  for  reasons  other  than  his  knowledge  of 
how  to  plan  a  hospital.  The  requirements  of  a  hospital  are  so  varied  that 
no  architect  or  commission  can  develop  the  best  in  hospital  construction 
unless,  in  addition  to  an  extensive  study  of  what  is  good  and  what  is  to  be 
avoided  in  existing  hospitals,  they  call  to  their  aid  and  freely  profit  bv  the 
advice  of  many  of  those  whose  lives  are  devoted  to  hospital  work,  who  have 
in  the  school  of  experience  discovered  the  good  and  the  bad  points  about  a 
hospital.  I  refer  to  the  heads  of  every  department  in  the  hospital,  from 
the  superintendent  down,  and  such  of  the  medical  profession  as  have  an 
interest  in  and  have  conscientiously  studied  the  subject.  It  also  now  and  then 
happens  that  the  architect  is  so  intent  upon  attaining  an  imposing  and 
architecturally  perfect  exterior  that  he  sacrifices  the  interior  to  the  detriment 
of  the  patients,  for  whose  benefit  the  hospital  was  created. 

While  what  I  have  said  is  true  in  the  majority  of  instances,  it  is  but  just 
that  I  should  qualify  my  remarks  by  stating  that  there  are  many  exceptions 
in  which  those  in  charge  have  done  everything  in  their  power,  and  proceeded 
along  correct  lines  to  attain  the  best  results.  I  believe  that  in  the  future  an 
eft'ort  will  be  made  by  most  of  those  who  have  charge  of  planning  hospitals 
to  gather  information  from  every  possible  source. 

I  have  carefully  gone  over  your  preliminary  plans  and  must  congratulate 
the  gentlemen  who  have  developed  them.  .\  few  minor  changes  can  easily 
be  made  by  your  supervising  architect  when  the  working  drawings  are 
])repared. 

In  closing  1  would,  from  my  experience  in  hospital  work,  commend  vour 
efforts  to  establish  an  U|)-t(i-date  hospital,  but  also  to  call  your  attention  to 
the  great  responsibilities  and  large  outlay  of  mcjney  that  it  involves,  both  in 
building  and  projjer  maintenance. 


I.  THE  MEDICAL  TREATMENT  OF  GRAVES'  DISEASE  WITH 
SPECIAL  REFERENCE  TO  THE  USE  OF  CORPUS  LUTEU^I 
EXTRACT.' 

By  Hi-kMAx  H.  HoppK.  A.M..  M.  D. 

Cincinnati 

The  corpus  luteuni  has  been  the  subject  of  much  study  in  recent  years 
and  much  light  has  been  thrown  upon  its  structure  and  origin,  since  Fraen- 
kel's  paper  in  1903.  Perhaps  the  most  exhaustive  and  critical  research  both 
as  to  the  origin,  structure  and  physiology  of  this  ductless  gland  has  been 
]iublished  by  Novak,  who  has  studied  its  relation  to  menstrual  disorders. 
Other  investigators  have  shown  that  the  corpus  luteum  has  not  only  an  influ- 
ence on  menstruation  and  pregnancy,  but  that  it  probably,  by  an  internal 
secretion,  which  is  poured  directly  into  the  circulation,  has  not  only  an  influ- 
ence on  the  development  and  the  function  of  the  mammary  gland,  but  that 
it  also  has  a  marked  influence  on  the  secondary  sex  characters  and  therefore 
on  the  metabolism  of  the  body  as  a  whole. 

Before  going  on  to  the  subject  of  the  relation  between  the  corpus  luteum 
and  the  thyroid  gland,  which  is  the  subject  of  this  paper,  let  us  consider 
briefly  what  we  know  of  the  corpus  luteum  to-day. 

We  know  that  the  normal  corpus  luteum  is  developed  from  the  Graafian 
follicle.  Whether  it  is  of  connective  tissue  or  epithelial  origin  has  been  the 
subject  of  quite  a  dispute,  but  Novak,  to  whose  article  I  refer  those  who  are 
interested  in  this  discussion,  concludes,  as  a  result  of  the  study  of  a  series  of 
137  ovaries  removed  by  operation,  and  especially  by  a  study  of  the  very 
earliest  stages  of  development,  that  it  is  epithelial  in  character  and  is  derived 
from  the  epithelial  cells  of  the  menibrana  granulosa  of  the  Graafian  follicles. 
In  this  view  he  confirms  the  earlier  studies  of  Meyer  and  the  work  of 
Sobotta,  who  prove  without  a  doubt  the  epithelial  origin  of  the  corpus  luteum 
in  the  lower  animals.  He  says:  "There  is  no  reasonable  doubt  of  the  origin 
of  the  lutein  cells  from  the  epithelium  of  the  menibrana  granulosa."  There 
are  two  kinds  of  specific  cells  in  the  corpus  luteuin,  namely,  the  lutein  cells 
and  the  paralutein  cells.  In  addition  these  cells  are  found  to  have  a  rich 
blood  supply,  the  cells  covering  a  very  rich  network  of  newly  formed  blood 
vessels. 

It  is  therefore  held  to-day  that  the  corinis  luteum  is  a  glandular  organ, 
and  that  the  epithelial  cells,  viz..  the  lutein  and  the  paralutein  cells,  ])our  their 
secretion  directly  into  the  blood  vessel  upon  which  they  are  embedded. 

The  corpus  luteum  therefore  is  a  ductless  organ  and  it  has  a  most  impor- 
tant function  in  regulating  the  sexual  life  of  woman.  It  does  this  probably 
by  secreting  a  chemical  agent  into  the  blood  stream.  The  efifect  of  this  chem- 
ical agent  is  a  local  one,  namely,  on  the  uterus,  and  ])erhaps  a  general  one, 

1. 

I'a.j,-   If 


HERMAN  H.  HOPPE 


affecting  the  mammary  glands  and  the  metabolism  underlying  the  develop- 
ment and  the  regulation  of  secondary  sexual  characteristics.  In  relation  to 
the  first  function,  viz.,  in  relation  to  the  uterus,  Novak  says :  "There  can 
be  but  little  doubt  that  the  corpus  luteum  possesses  at  least  a  dual  function : 
(a)  The  causation  of  menstruation;  (b)  the  preparation  of  the  endometrium 
and  the  fixation  of  the  ovum  in  the  earliest  stage  of  pregnane^-."  Novak  sug- 
gests that  the  lutein  cells  stands  in  relation  to  the  production  of  menstrua- 
tion, and  the  paralutein  cells  to  the  function  of  ovum  fixation.  "I  may  sim- 
ply state  that  in  nineteen  corpora  lutea  exhibiting  marked  development  of 
the  paralutein  cells,  all  except  a  few  were  removed  from  patients  who  gave 
histories  of  profuse,  and  in  a  few  instances  of  irregular  menstruation.  It  is 
curious  to  note  that  many  of  these  patients  were  sterile." 

It  seems  therefore  to  have  been  demonstrated  that  the  secretion  of  the 
corpus  luteum  has  an  all-important  role  in  normal  menstruation  and  in 
normal  pregnancy.  It  would  seem  reasonable  therefore  to  conclude  that  a 
functional  decrease  or  a  functional  increase  may  cause  amenorrhea  or 
amenorrhagia. 

Being  one  of  the  ductless  glands,  the  ovary,  perhaps  through  the  corpus 
luteum,  stands  in  relation  to  all  the  other  ductless  glands,  and  the  ovary  is 
the  avenue  through  which  all  the  other  ductless  glands  exert  their  influence 
on  the  functions  of  the  female  generative  organs. 

That  the  corpus  luteum  also  exerts  an  influence  on  the  mammary  glands 
and  the  metabolism  underlying  secondary  sexual  characteristics  is  at  least 
possible.  This  is  indicated  by  the  research  work  of  Seitz-Wintz  and  Finger- 
hut,-  who  think  that  they  have  isolated  two  active  principles  for  the  corpus 
luteum.  which  they  say  are  opposite  in  their  activity  in  relation  to  the  func- 
tions of  menstruation  and  pregnancy. 

i.  Luteolipoid  which  inhibits  menstruation  and  when  injected  hypo- 
dermically  diminishes  the  excessive  flow. 

ii.  Lipamin,  which  in  animal  experiments  stimulates  the  development  of 
the  sexual  organs  and  when  given  hypodermatically  in  amenorrhea  brings 
on  the  menstrual  flow.  Similar  observations  on  the  relation  between  the 
corpus  luteum  and  the  mammary  gland  have  been  made  by  Hammond  and 
Marshall,  and  very  interesting  observations  on  the  relation  between  the 
corpus  luteum  and  secondary  sex  characteristics  were  made  by  Pearl  and 
Surface. 

Can  we  regard  the  internal  secretion  of  the  corpus  luteum  as  the  specific 
internal  secretion  of  the  interstitial  tissue  of  the  ovary?  Is  there  any  other 
internal  secretion  of  the  ovary,  which  is  separate  and  distinct  from  that  of 
the  corpus  luteum?    This  question  as  yet  is  unanswered. 

Now  let  us  consider  what  the  relations  between  the  thyroid  and  the 
corpus  luteum  may  be,  and  how  a  disturbance  of  this  harmonious  relation 
may  result  in  hyperthyroidism. 


RANSOHOFF  MEMORIAL  VOLUME 


It  is  {]uite  agreed  tliat  the  regulation  of  metabolism  is  the  function  of  the 
ductless  glands,  and  that  the  tli\  roid"s  chief  function  is  the  regulation  of  the 
proteid  metabolism.  At  any  rate  we  conclude  this  to  be  the  case,  because  in 
Graves'  disease  the  proteid  metabolism  is  greatly  increased  and  in  myxedema 
it  is  greatly  diminished. 

According  to  the  physiological  action.  Falta  divides  the  ductless  glands 
into  two  groups,  the  acceleratory  group  and  the  retardative  group,  in  so  far 
as  they  produce  acceleratory  or  retarding  hormones.  These  groups  through 
their  hormones  exert  an  antagonistic  efTect  on  the  metabolic  processes  of 
the  body.  Thus,  for  example,  the  hormone  of  the  thyroid  gland  is  regarded 
as  an  acceleratory  catabolic  and  dissimilatory.  It  quickens  metabolism  and 
increase  excitability.  This  w^e  see  in  Graves'  disease,  whereas  the  absence 
of  this  hormone,  which  we  see  in  myxedema,  causes  an  arrest  of  growth, 
which  is  regarded  as  the  effect  of  the  inhibition  of  metabolism.  Opposed 
to  this  action  is  the  group  of  glands  with  retardation,  anabolistic  or  assimila- 
tory  hormones."  They  build  u])  and  stimulate  assimilation.  The  interstitial 
glands  have  also  this  function  (  interstitial  tissue  of  the  testicles,  and  the 
corpus  luteum?). 

On  this  theory  one  could  explain  the  development  of  the  Graves  complex 
as  being  the  result  of  the  degeneration  of  the  Graafian  follicle.  The  Graafian 
follicle,  according  to  this  hypothesis,  does  not  reach  maturity,  it  does  not 
bur^t.  but  it  degenerates,  undergoes  lic[uefaction  and  disappears.  The  corjnis 
luteum  therefore  is  not  formed  and  since  the  specific  internal  secretion  of  the 
ovary  is  the  function  of  the  inature  and  developed  corpus  luteum,  this  inter- 
nal secretion  is  not  produced  and  the  chain  of  ductles  glands  is  unbalanced. 

The  next  point  to  consider  is  what  causes  the  clinical  manifestations  of 
Graves'  disease?  It  is  needless  to  enter  here  into  a  critical  consideration  of 
all  the  various  theories:  the  psychogenic,  bulbar,  cardiac,  sympathetic  and 
the  thyroid  theory. 

We  will  consider  the  latter  theory  only,  because  in  the  light  of  the  favor- 
able results  obtained  by  surgery,  it  seems  to  be  the  only  tenable  theory.  This 
is  also  fortified  by  our  present  knowledge  of  the  physiology  of  the  thyroid 
and  of  the  secretions  of  and  interrelation  of  the  whole  chains  of  endocrine 
glands,  and  we  believe  that  the  thyroid  theory  explains  more  completely  and 
satisfactorily  the  symptomatology  of  Graves'  disease  than  any  of  the  others. 
The  next  consideration  is  as  to  whether  the  thyroid  merely  gives  out  an 
excessive  secretion,  or  whether  the  secretion  is  vitiated.  Is  there  merely 
hyperthyroidism  or  dysthyroidism?  Are  we  dealing  with  a  perverted  .secre- 
tion or  with  an  excessive  secretion?  The  results  obtained  surgically  would 
seem  to  indicate  that  the  symi)toin-c()m]ilex  results  frnni  an  excessive  secre- 
tion. 

According  to  Falta,  poisoning  and  excessive  function  are  merely  synony- 
mous terms;  we  do  not  need  to  assume  a  per\erted  function  of  the  thyroid 


HERMAN  H.  HUFl'E 


in  Graves'  disease.  A  normal  secretion  poured  into  the  circulation  in 
excess  will  poison  the  body.  Kalta  calls  our  attention  to  adrenalin  poison- 
ing as  a  fitting  example.  We  undoubtedly  have  in  Graves'  disease  pluri- 
glandular symptoms,  but  we  need  not  assume  from  this  the  existence  of  pluri- 
glandular disease,  for  we  cannot  have  a  marked  hyperfunction  of  any  one  of 
the  ductless  glands  without  disturbing  the  functions  of  all  or  most  of  them. 
(  )ur  clinical  experience  and  the  theory  on  which  the  use  of  the  extract  of 
corpus  luteum  is  based  is  that  Graves'  disease  and  hypothyroidism  arc 
equivalent  terms. 

It  is  a  fairly  well-established  theory,  and  we  have  quoted  Falta  above  to 
the  efifect  that  there  is  an  antagonistic  action  on  the  metabolism  of  the  body, 
between  the  thyroid  glands  and  the  interstitial  sex  glands.  We  would  like 
to  suggest  as  the  basis  of  clinical  experience — the  treatment  of  Graves' 
disease — that  the  internal  secretion  of  .the  corpus  luteum  has  an  inhibitory 
effect  on  the  thyroid  secretion,  and  that  hyperthyroidism  is  an  expression  of 
a  dysfunction  of  the  corpus  luteum  in  the  female  and  of  the  interstitial 
glands  of  the  testicle  in  the  male.  This  view  is  also  held  by  Claude  and 
Gougerot,  who  speak  of  Graves'  disease  as  being  due  to  a  hypovarie — a 
hypovarial  disease. 

The  most  serious  theoretical  objection  to  this  theory  is  that  we  rarely  see 
a  typical  Graves'  symptom-complex  follow  the  removal  of  the  ovaries  and 
testicles.  We  know  however  that  after  castration  in  both  the  male  and  in 
the  female  and  during  pregnancy,  there  is  a  marked  increase  in  the  size  of 
the  pituitary  gland  and  this  compensatory  enlargement  may  mean  a  physio- 
logical compensation  of  function.  This  is  borne  out  by  an  observation  which 
I  made  in  a  very  acute  case  of  Graves'  disease  in  a  man,  in  whom  the  admin- 
istration of  an  extract  of  the  anterior  lobe  of  the  pituitary  gland  was  followed 
by  marked  amelioration  of  the  .symptoms.  Renon  and  Delille  saw  a  Graves' 
disease  symptom-complex  disappear  as  the  result  of  the  simultaneous  admin- 
istration of  pituitary  and  ovarian  extract. 

Clinically  there  is  an  abundance  of  proof  that  the  sexual  apparatus  and 
the  thyroid  are  closely  associated.  Graves'  disease  is  found  almost  entirely 
among  women,  cases  in  men  being  rather  rare.  Women  are  affected  at  least 
six  times  as  often  as  men  and  in  my  experience  the  proportion  is  still  larger. 
Puberty  is  a  very  favorable  time  for  its  development.  In  the  second  place 
there  is  almost  always  a  disturbance  of  menstruation ;  during  the  periods  of 
exacerbation  es])ecially,  we  find  \ery  often  amenorrhea  or  deficietU  men- 
struation. In  women  it  occurs  almost  exclusively  during  the  period  of 
sexual  life,  being  very  rare  before  the  age  of  puberty  and  verv  rarely  devel- 
oped after  the  menopause. 

Pregnancy  has  a  decided  influence  on  the  course  of  Graves'  disease. 
Many  women  with  Graves'  disease  do  not  conceive  at  all.  In  diher  cases 
we  notice  a  decided  improvement  during  pregnancy.  In  one  of  mv  cases 
the  patient  was  comparatively  well  during  one  pregnancy,  was  rather  bad 

Pui/c  jn;i 


RAXSOHOFF  MEMORIAL  lOLUME 


during  a  second,  whereas  an  acute  and  violent  relapse  occurred  during  a 
period  of  amenorrhea,  but  she  improved  for  a  while  under  the  effect  of 
corpus  luteum  and  then  relapsed  so  acutely  as  to  necessitate  surgical  interven- 
tion. Another  patient  who  had  a  mild  attack  of  Graves'  disease  at  the  age 
of  sixteen,  which  disappeared  after  a  short  period  of  treatment,  suddenly 
had  a  very  acute  relapse  during  her  first  pregnancy  ten  years  later,  which 
continued  up  to  delivery,  all  symptoms  disappearing  very  soon  after  the  birth 
of  the  child.  This  rather  paradoxical  relation  of  pregnancy  and  Graves' 
disease  may  be  explained  by  the  fact  that  when  the  corpus  luteum  of  preg- 
nancy is  normally  developed  there  is  an  improvement  in  the  symptoms  of 
the  patient  and  when  the  corpus  luteum  of  pregnancy  is  functionally  deficient 
there  is  an  exacerbation  of  the  symptoms.  This  is  very  readily  understood 
when  we  consider  the  great  role  which  the  corpus  luteum  plays  during  the 
early  part  of  pregnancy,  at  least.  On  the  same  grounds  we  can  explain  the 
exacerbations  and  remissions  which  occur  in  the  course  of  the  ordinary 
cases  of  Graves'  disease.  When  the  rupture  of  the  Graafian  follicle  is  fol- 
lowed by  a  normal  corpus  luteum  the  symptoms  ameliorate  and  vice  versa. 

The  interrelation  of  the  thyroid  and  ovary  is  also  shown  by  those  mild 
cases  of  myxedema,  which  show  a  normal  thyroid  metabolism  during  the 
interval  between  the  menstrual  periods  and  an  active  myxedema  during  the 
period.  It  would  seem  to  indicate  that  the  corpus  luteum  exerted  an  inhibi- 
tory effect  on  the  thyroid  in  these  cases,  and  that  the  thyroid  which  was 
capable  of  performing  its  function  fairly  normally  during  the  inter-menstrual 
l)eriod  lost  its  ability  to  do  so  during  the  period  of  greatest  activity  of  the 
corpus  luteum.* 

Is  it  not  possible  that  the  same  interrelation  between  the  thyroid  and  the 
corpus  luteum  is  at  least  suggested  by  the  symptom-complex  of  hyperthyroid- 
ism, obesity  and  .sterility.  At  times  in  these  cases  the  use  of  thyroid  extract 
is  followed  by  pregnancy.  We  also  know  that  absolute  cretins  never  come 
to  puberty. 

I  was  impelled  to  use  the  corpus  luteum  in  a  very  acute  case  of  Graves' 
disease  three  years  ago,  in  which  there  was  a  slight  enlargement  of  the 
thyroid,  a  loss  of  weight  of  over  sixty  pounds,  and  in  which  a  prolonged 
rest  cure  and  the  ordinary  Forchheimer  treatment  produced  little  or  no 
improvement.  The  woman  had  been  married  twenty-five  years,  had  never 
been  pregnant  and  menstruation  was  now  suspended  for  a  year.  The  use 
of  the  ext.  corpus  luteum  by  mouth  was  followed  by  such  rapid  improve- 
ment in  the  general  nervous  symptoms  and  the  cardio-vascular  symptoms 
especially,  in  a  very  few  days,  that  I  decided  to  give  the  corpus  luteum  an 
extensive  test.    This  first  patient  made  a  complete  clinical  recovery. 

In  the  past  two  or  three  years  I  have  treated  about  twenty  cases  of 
Graves'  disease.  The  ordinary  Forchheimer  treatment  was  attended  with 
only  indifferent  success.     The  combination,  however,  of  the  quinine  hydro- 

4.     E.  HcrtoRhe.   Medical  Recor.l.   1914 


HERMAN  H.  HOPPE 


bromate,  ext.  belladonna  with  the  ext.  corpus  kiteum  was  found  to  be  rap- 
idly beneficial  in  nearly  all  the  cases  and  the  improvement  was  usually  so 
rapid  and  so  marked,  in  a  few  days  to  a  week,  to  convince  me  that  rest,  diet, 
hygienic  measures,  all  of  which  I  had  used  for  twenty  years  before,  could  not 
account  for  the  result,  but  that  the  corpus  luteum  was  the  active  therapeutic 
agent. 

I  wish  to  emphasize  the  fact  that  the  above  were  all  clinically  cases  of 
Graves'  disease,  no  border-land  doubtful  cases  of  hyperthyroidism,  in  which 
the  diagnosis  might  depend  upon  the  bias  of  the  observer.  Twelve  of  these 
cases  were  of  the  more  se\ere  type  with  rapid  emaciation,  great  nervous 
excitability,  rapid  pulse,  pulsating  thyroid  gland,  diarrheas,  etc.  The  other 
eight  were  moderately  severe  cases.  ()f  the  very  acute  cases,  one  died.  I 
saw  this  patient  a  week  beft>re  her  death,  after  her  cases  had  been  in  an  acute 
state,  with  marked  mental  symptoms  for  three  months.  She  had  the  treai- 
ment  for  only  a  week  and  I  saw  her  but  once,  and  she  was  practically  mori- 
bund at  the  time.  A  second  patient  in  this  group,  who  had  an  attack  several 
years  before,  at  first  improved  both  in  weight  (she  had  lost  thirty  pounds), 
in  her  general  nervous  condition,  and  especially  in  the  pulse  rate,  which 
dropped  from  120  to  84  per  minutes  in  the  course  of  ten  days.  She  con- 
tinued to  do  well  under  the  treatment  for  three  months  and  then  while 
taking  the  ext.  corpus  luteum  had  a  very  acute  exacerbation  with  a  pulse 
rate  of  nearly  200  and  signs  of  great  exhaustion  and  collapse.  She  was 
operated  upon  and  the  partial  removal  of  the  thyroid  was  followed  by  relief, 
but  not  by  a  cure,  all  of  the  symptoms  of  Graves'  disease  being  present  eight 
months  after  the  operation. 

One  other  very  acute  case  was  not  benefited  by  the  treatment  according 
to  her  statement,  although  the  cliiiical  record  of  her  case  shows  that  her 
pulse  rate  at  the  first  examination  was  140  beats  per  minute,  and  a  week 
later  was  108.  She  discontinued  treatment  and  when  seen  at  m\-  re(|uest  a 
year  later  was  in  a  very  acute  state  of  Graves'  disease. 

One  of  the  exceedingly  acute  cases  was  a  man,  the  only  one  treated. 
Bed  rest  improved  him  for  a  while,  but  later  on  he  had  a  very  acute  relapse. 
Not  knowing  of  any  reliable  preparation  of  the  interstitial  glands  of  the 
testicle,  I  placed  this  man  on  the  ext.  of  the  anterior  lobe  of  the  pituitary 
gland  and  he  showed  marked  improvement  while  under  this  treatment. 
Later  on  he  passed  from  under  my  supervision. 

All  of  the  other  cases  have  improved  under  the  treatment,  all  of  them 
have  the  ordinary  routine  treatment  and  in  addition  to  hygienic  measures 
and  partial  rest  I  combine  the  extract  of  corpus  luteum  0.12  with  quinine 
hydrobrom.  0.12  and  ext.  belladonna  0.006  per  dose. 

Only  one  of  these  cases  is  really  cured.  But  all  the  others  are  improved 
and  very  comfortable.  The  most  notable  impro\ement  and  the  one  most 
quickly  noticed  are  the  the  cardio-vascular  symitoms.  The  pulse  rate  drops 
very  quickly  and  the  disagreeable  sym])t(inis  caused  by  the  disturbance  of 


RAXSOHUl'f  MEMORIAL  VOLUME 


circulation  quickly  subside.  Then  the  general  nervous  irritability  dimin- 
ishes and  the  ]iatients  all  return  to  a  more  or  less  normal  condition.  I  have 
found,  however,  that  the  i)atients  often  show  a  tendency  to  relapse  and  have 
remissions  if  they  stop  the  ext.  corpus  luteum.  If  the  above  theory  of  the 
relation  of  the  corpus  luteum  and  the  thyroid  gland  is  correct,  this  is  what 
we  would  expect.  If  Graves'  disease  is  synonymous  with  hvpovarie,  with  a 
dysfunction  or  a  diminished  function  of  the  corpus  luteum.  we  would  get 
results  just  as  those  recorded  above.  The  Graves'  symptom-complex  arises 
as  a  result  of  a  defective  or  deficient  secretion  of  the  corpus  luteum.  If  we 
replace  the  deficiency  by  the  use  of  ext.  of  corpus  luteum  we  relive  the 
patient  and  impro\e  her  condition.  \\'e  cannot,  however,  change  the  defec- 
tive biological  activity  of  the  ovary  and  make  a  defective  ovary  produce  a 
normal  corpus  luteum.  ,\nd  this  is  the  experience  in  my  cases.  Nearly  all 
of  them  require  the  extract  continuously,  sometimes  one  dose  of  the  above 
combination  per  dav  will  suffice.  Others  require  two  or  three  doses  per 
day.  In  some  of  the  cases  there  are  periods  of  months  when  they  are 
apparently  free  from  all  symptoms  of  Graves'  disease  and  we  may  interpret 
these  periods  of  remission  as  occurring  during  the  time  when  the  ovaries 
]}roduce  normal  corpus  luteum. 

I  believe  that  Graves'  disease  in  this  respect  can  be  compared  with  luyxe- 
dema  and  hypothyroidism ;  as  long  as  we  administer  thvroid  extract  in 
these  two  conditions,  the  patients  are  fairly  normal.  As  long  as  we  admin- 
ister corpus  luteum  in  Graves'  disease  or  in  the  ])eriods  of  exacerbation,  the 
jiatient  is  improxefl  and  can  be  kept  in  a  fairly  normal  state. 

lilBUOGU.VPllV. 

I,.  Fiacnkrl.     .\nh.   f.  C.ynaik..   1903.  Vol.  58.  page  4.i>!. 

v..    Xov.nk.      Join.    .\.ii.    Med.    .\s5n..    1916.   Vol.    67.    paRf    1-'8.V 

FaltaMeyer.      Tlie   Ductless  C.landular  Diseases.     P.    Blakistoirs  Son  and   Co.      -'ml  edilian. 

Seitz-Wintz  and  Fingeihut.     Munch.   Med.   W'ochcnsch..  1914.  No.  30.,11. 

Hammonds  and  Marshall.     Proceed.   Royal  Society.  London   (B).  1914.  page  Ml. 

Pearl   and   Surface.      Science.    191.S.    Vol.    XU,   page   61,=i. 

Claude  and  Gougerot   (Falta).     C.az.  d.  hop.   191.'.  No.  57.  849. 

E.  Hcrtoghe.     Med.  Record,   1914. 


II.    THE  TREATMENT  OF  HYPERTHYROIDISM  \\TTH  CORPUS 
LUTEUM:     A  SECOND  REPORT.* 

H.  H.  HcippK,  A.  M.,  M.  D. 

Cincinnati 

'I'hc  treatincnt  of  Graves'  disease  is  an  ever  interesting  and  important 
topic  for  discussion. 

The  fact  that  there  is  hardly  a  meeting  of  surgeons  without  a  paper  or 
even  a  symposium  on  the  surgical  treatment  of  Graves'  disease  and  the  wide- 
spread discussion  of  the  papers  shows  that  the  surgeons  have  not  solved  the 
problem,  notwithstanding  the  vogue  which  the  surgery  of  the  thyroid  enjoys 
at  [iresent. 

The  numerous  methods  of  treatment  on  a  i)Urely  hygienic  and  medical 
basis  and  the  published  results  of  treatment  is  also  a  proof  that  the  results 
of  treatment  from  a  purely  medical  stand])oint  are  far  from  being  satisfac- 
tory. Both  the  surgical  and  medical  methods  of  attack  are  defective  for 
the  reason  (hat  both  approach  the  problem  from  a  symptomatic  standpoint. 

THK  \VE.\KNESS  OF  SURGICAL  AND  Dl^UG  TRE.\TME.\T. 

The  weakness  of  the  surgical  approach  is  that  its  aim  is  to  remove  the 
thyroid  gland  which  is  not  the  primary  scat  of  disturbance  but  merely  an 
expression  of  disordered  function,  whose  causative  seat  is  located  in  some 
other  portion  of  the  body.  This  accounts  for  the  fact  that,  while  undoubt- 
edly many  cases  are  benefitted  by  surgical  intervention  and  many  distressing 
symptoms  are  relieved,  many  of  the  patients,  months  and  years  after  the 
operation,  still  show  most  of  the  classical  signs  of  the  disease,  notwithstand- 
ing the  removal  of  the  thyroid  gland.  The  operation  has  merely  made  the 
patient's  condition  more  tolerable. 

The  purely  drug  treatment  inclusive  of  the  treatment  for  intestinal  auto- 
intoxication is  not  often  successful  because  it  is  purely  symptomatic.  What- 
ever results  are  obtained  are  the  results  of  nature's  own  recuperative  powers, 
assisted  by  rest  and  other  hygienic  measures. 

The  ideal  treatment  should  be  based  upon  an  etTort  to  find  and  remove 
the  cause  of  hyperthyroidism. 

THE  CAUSE  OE  EXCESSIVE  THYROID  EUNCTIO.V. 
It  is  generally  conceded  that  hyperthroidism  is  an  expression  of  an  unbrd- 
anced  state  of  the  chemical  mechanism  of  the  endocrine  glands.  The  over- 
acti\ity  of  the  thyroid  is  never  primary.  It  is  unthinkable  that,  without  any 
apparent  cause,  there  should  suddenly  be  present  a  state  of  excessive  func- 
tion of  the  thyroid.     Hence  our  first  approach  toward  a  rational  treatment 

♦Read  bffure  the  Section  on  Nervous  ami  Mental  Diseases  of  the  Ohio  State  Medical  .Vssociv 
lion.  during  the  Seventv-fourth  Annual  Meeting,  at  Toledo,  June  1,  1920.  From  The  Ohio  State 
.Medical   Journal.   October,    19J0. 


RAXSOHOFf  .MEMORIAL  VOLUME 


of  hyperthyroidism  should  be  an  endeavor  to  discover  the  cause ;  why  the 
function  of  the  thyroid,  which  previously  has  been  normal,  should  now  be 
excessive. 

The  second  indication  of  treatment  is  to  overcome  and  remove  the  effects, 
on  the  body  as  a  whole,  of  the  over-activity  of  the  thyroid  gland. 

The  results  of  the  over-activity  of  the  thyroid  manifest  themselves  grad- 
ually and  progressively  on  nearly  all  the  organs  and  functions  of  the  body. 
A  whole  train  of  signs  and  symptoms  which  may  be  looked  upon  as  a  result 
of  the  presence  in  the  circulation  of  an  excessive  amount  of  thyroid  secre- 
tion, gradually  develops,  which  is  an  expression  of  disordered  metabolism 
and  hence,  of  parenchymatous  changes  of  the  tissues  of  all  the  organs  of  the 
body.  Many  of  the  efifects  of  this  disordered  function  persist  even  after  the 
thyroid  has  been  removed.  These  changes,  primarily  the  result  of  toxic 
action  of  thyroid  over-activity,  persist  even  after  all  possiblity  of  thyroid 
action  has  been  removed  and  hence  demand  special  treatment,  irrespective 
of  the  proximal  cause.  The  persistence  of  these  syiiiptoiiis  is  the  best  proof 
that,  although  they  arc  originally  caused  by  hyfcrtliyroidisiii.  the  later  condi- 
tion is  merely  a  secondary  cause,  the  primary  cause  being  some  other  remote 
organic  or  functional  derangement  of  one  of  the  otiier  endocrine  glands. 
If  this  were  not  true  such  signs  as  exophthalmos,  tachycardia,  tremor,  and 
excessive  metabolism,  should  not  jiersist  years  after  the  removal  of  the 
thyroid  gland. 

GEXER.\L  COXSIDERATiOXS  OF  TKE.\TM1'\T. 

\\'e  shall  endeavor  to  place  before  you  our  experience  in  the  treatment 
of  hyperthyroidism  extending  over  a  period  of  five  years  and  embracing 
about  fifty  cases.  These  embrace  all  degrees  of  hyperthyroidism  from  the 
mild  to  the  most  acute.  None,  however,  were  doubtful  cases,  the  diagnosis 
in  all  being  based  upon  the  classical  symptoms  plus  the  presence  of  a  distinct 
bruit  in  the  thyroid  gland.  We  believe  that  the  good  results  in  the  treatment 
of  these  cases  were  due  to  the  use  of  the  extract  of  corpus  luteum  : 

In  treating  this  subject  let  us  consider: 

1.  The  function  of  the  thyroid  gland. 

2.  The  relation  of  the  thyroid  to  the  other  endocrine  glands. 
,1    The  histology  and  the  function  of  the  corpus  luteum. 

4.    The  clinical  results  obtained  in  the  treatment  of  hyperthyroidism  with 
the  corpus  luteum  and  the  theory  on  which  the  treatment  is  based. 

THE  FUXCTIOX  OF  THE  THVKOH). 
1.  It  seems  to  be  fairly  well  establi.shed  that  the  regulation  of  metab- 
olism is  one  of  the  chief  fimctions  of  the  ductless  glands  and  that  the  special 
function  of  the  thyroid  is  the  regulation  of  proteid  metabolism.  W'e  see, 
therefore,  an  increase  in  basal  metabolism  in  hyperthyroidism  and  a  decrease 
in  basal  metabolism  in  hypothyroidi>m.    Felta  divides  the  ductless  glands  into 


HERMAN  H.  HOPPE 


two  groups  according  to  their  physiological  function,  the  acceleratory  group 
and  the  retardative  group.  Through  their  hormones  these  glands  exert  an 
antagonistic  effect  on  the  metabolism  of  the  body. 

The  thyroid  gland,  through  its  hormones,  quickens  metabolism  and 
increases  excitability.  We  see  this  typically  in  hyperthyroidism  in  which  an 
excess  of  hormones  is  produced.  In  myxoedema  we  have  an  arrest  of 
growth  due  to  an  inhibition  of  metabolism,  because  of  a  deficiency  in  pro- 
duction of  the  hormones  of  the  thyroid. 

RELATION  TO  OTHER  ENDOCRINE  GL.ANDS. 

2.  Opposed  to  the  acceleratory  group  of  glands  are  those  of  the  second 
group  which  have  the  opposite  or  retardative  action.  They  build  u]i  and  stim- 
ulate assimulation.  In  this  group  we  have  the  interstitial  glands,  the  testicles 
and  the  ovary. 

We  have,  therefore,  an  antagonistic  action  between  (he  thyroid  gland  and 
the  sex  glands  and  we  will  assume  for  the  present,  with  an  cfTort  later  on  to 
ofifer  proof,  that  the  sex  glands  act  as  an  inhibitory  agency  on  the  thyroid 
gland  and  that  when  there  is  an  absence  of  the  specific  secrete  of  the  inter- 
stitial, sex  glands  and  the  other  ductless  glands  are  unable  to  make  the 
compensation,  we  will  have  an  excessive  function  of  the  thyroid  gland. 

FUNCTION  OF  THE  CORPUS  LUTEUM. 

3.  We  know  that  the  specific  hormone  of  the  testicle  is  produced  by  the 
interstitial  tissue.  For  the  ovary,  the  proof  of  an  interstitial  secretory  tissue 
has  not  been  so  well  established.  We  shall  try  to  offer  proof  that  the  spe- 
cific hormone  of  the  ovary  is  produced  by  the  corpus  luteuni. 

Fraenkel  published  a  paper  on  the  structure  and  origin  of  the  cor|nis 
luteum,  in  1903.  Novack  studied  the  relation  of  the  corpus  luteum  to  men- 
strual disorders  and  his  research  into  its  origin,  structure  and  physiology 
is  most  critical  and  exhaustive.  Other  investigations  have  shown  that  the 
corpus  luteum  influences  the  development  and  function  of  the  mammary 
gland  and  also  that  it  affects  the  developments  of  secondary  sex  characters. 

Let  us  consider  somewhat  in  detail,  what  we  know  of  the  corpus  luteum 
to-day.  In  a  previous  article  we  sought  to  establish  the  fact  that  the  cor]nts 
luteum  secretes  the  specific  hormone  of  the  ovary  and  is  therefore  a  duct- 
less gland.  We  know  that  the  corpus  luteum  is  the  final  stage  of  the  devel- 
opment of  the  Graafian  follicle.  Novak  made  a  careful  study  of  one  hun- 
dred and  thirty-seven  ovaries  which  had  been  removed  during  operation  on 
the  pelvic  organs  and  he  concludes  that  the  corpus  luteum  is  epithelial  in 
character  and  that  it  is  derived  from  the  epithelial  cells  of  the  membrana 
granulosa  of  the  Graafian  follicles.  Myer  and  Sobotta  had  ])reviously  come 
to  the  same  conclusion  as  to  the  origin  of  the  corpus  luteum  in  lower  animals. 

The  corpus  luteum  contains  two  kinds  of  specific  cells — the  lutein  cells 
and  the  paralutein  cells.     These  cells  cover  a  very  rich  network  of  newly 

Page    l".'i 


RAXSOHOFf  MEMORIAL  rULUME 


formed  blood  vessels.  It  is  held,  therefore,  that  these  cells,  the  lutein  and 
paralutein  cells,  being  epithelial,  have  a  secretory  function,  that  they  pour 
their  secretion  directly  into  the  blood  vessels  upon  which  they  are  imbedded 
and  (hat  the  corpus  luteum  is  therefore  a  ductless  organ. 

The  most  important  function  of  the  corpus  luteum  is  the  reKulatiim  of 
the  sexual  life  of  woman.  The  hormone  of  the  corpu^  luteum  acts  in  a 
two-fold  way: 

(a)  A  local  action  on  the  uterus  and  perhaps  the  placenta. 

(b)  A  general  one,  liz.,  the  regulation  of  the  metabolism  underlying  the 
development  of  the  secondary  sexual  characteristics,  seen  especially  perhaps 
in  the  mammary  glands. 

In  regard  to  the  first  function  Novak  says:  "There  can  be  but  litt> 
doubt  that  the  corpus  luteum  has  at  least  a  dual  function,  (a)  the  causatioi- 
of  menstruation;  (b)  the  preparation  of  the  endometrium  and  the  fixation 
of  the  ovum  in  the  earliest  stages  of  pregnancy."  Xo\ak  goes  further  and 
states  that  he  has  observed  in  ovaries  in  which  the  paralutein  cells  were 
present  in  large  numbers  in  the  corpora  lutea.  the  patients  suffered  from  pro- 
fuse menstruation,  irregular  periods  and  sterility.  He  believes  that  the  luiein 
cells  stand  in  relation  to  menstruation  and  that  the  paralutein  cells  have  som: 
relation  to  ovum  fixation. 

Seitz.  W'intz  and  Fingerhut  think  that  they  have  isolated  the  hormone'; 
of  the  corpus  luteum  and  claim  that  it  secretes  two  active  principles  which 
are  opposite  in  their  activity  in  relation  to  the  functions  of  menstruation  and 
pregnancy. 

1.  Luteolipoid  which  has  an  inhibitory  influence  on  menstruation  and 
when  injected  hypodennically  diminishes  the  excessive  flow  in  menorrhagia. 

2.  Lipanin,  which  in  animal  experiments,  stimulates  the  development  of 
the  sexual  organs  and  in  human  beings  when  administered  hyi)i)dermically  in 
amenorrhoea  brings  on  the  menstrual  flow. 

Hammond  and  Morhall  ha\e  made  observalion>  on  the  relation  between 
the  corpus  luteum  and  nianunary  glands  and  F'earl  and  Surface  on  the  sec- 
ondary sexual  characteristics. 

It  seems  demonstrated,  therefore,  that  the  corpus  luteum  ha>  an  all  im- 
portant influence,  not  only  on  menstruation  and  jiregnancy.  but  also  on  the 
general  metabolism  of  the  bodv.  in  so  far  as  the  secondary  sexual  charac- 
teristics are  concerned.  There  can  be  no  doubt  that  other  organs  of  internal 
secretion  also  have  an  influence  on  the  regulation  of  the  metabolism  under- 
lying secondary  sexual  characteristics  and  that  these  organs  stand  in  rela- 
tion to  ovarian  activity  and  that  they  are  therefore  in  relation  to  the  corpus 
luteum  and  that  the  latter  organ  i>  therefore  the  avenue  ihmugh  which  the 
other  ductless  glands  exert  their  influence  on  tlie  functions  of  the  female 
generative  organs. 

If  these  contentions  of  .Xovak,  Me\er  :uk1  Snbatta.  that  the  corjius  luteum 
is  an  epithelial  gland  and  that  according  to  Novak  its  function  is  to  regulate 


Page 


HERMAN  H.  HOPPE 


menstruation  and  ovum  fixation,  and  if  the  observation  of  Seitz,  Wintz, 
Fingerhut,  Hammond,  Marshall,  Pearl  and  .'Surface  on  its  relation  to  sex 
characteristics  and  mammary  development  are  true,  then  there  is  at  least 
some  proof  that  there  must  be  a  specific  secretion  poured  from  the  cells  of 
the  corpus  luteum  into  the  general  circulation  and  that  therefore,  the  corpus 
luteum  is  a  ductless  gland  and  secretes  the  specific  hormone  of  the  inter- 
stitial tissue  of  the  ovary. 

A  defective  development  of  the  corpus  luteum,  therefore,  would  tend  to 
produce  a  lack  of  balance  of  the  endocrine  system. 

IXTKR-RKLATIOX   BETWEEN  THE  THYROID   .AND  OVAin'. 

We  know  that  there  is  often  a  lack  of  proper  development  of  the  Graafian 
follicle.  In  these  cases  the  follicle  does  not  reach  maturity,  it  does  not  burst, 
but  degenerates,  undergoes  liquifaction  and  disappears — the  corpus  luteum 
is  not  formed.  If  the  corpus  luteum  is  not  formed  the  specific  hormone  of 
the  ovary  is  lacking  and  the  chain  of  ductless  glands  is  unbalanced.  \Vhat 
proof  have  we  to  uphold  Felta's  contention  that  there  is  a  relation  and 
perhaps  an  antagonistic  relation  between  the  thyroid  and  the  ovary? 

We  have  seen  above  that  Felta  places  the  thyroid  gland  in  the  group  of 
those  glands  whose  hormones  accelerate  the  metabolism  of  the  body  by 
increased  ovidation  and  increased  excitability  of  the  tissues,  whereas  he 
places  the  hormones  secreted  by  the  interstitial  tissues  of  the  sex  organs  in 
the  antagonistic  group,  I'ic,  those  whose  function  is  to  build  up  instead  of 
breaking  down,  hormones  whose  function  is  anabolistic  instead  of  katabolis- 
tic — assimilatory  and  retardative  in  function. 

Our  therapy  is  based  upon  the  antagonistic  action  between  ili\niitl  and 
ovary  or  corpus  luteum  which  we  consider  the  specific  endocrine  uland  of 
the  ovary. 

Clinicall}'  there  is  abundant  proof  of  the  interrelation  of  thyroid  and  sex 
life.  In  man  the  sexual  function  is  an  incident.  In  woman  sexual  function 
is  the  chief  function  of  metabolism.  We  find,  therefore,  that  disturbance 
of  the  thyroid  activity  in  adults  is  found  chiefly  among  women.  Women  are 
affected  at  least  six  times  oftener  than  men  and  in  my  experience  the  pro- 
portion of  women  affected  is  still  greater.  In  women.  Graves'  disease  occurs 
almost  always  during  the  period  of  sexual  life.  It  begins  very  often  around 
puberty  and  its  course,  especially  during  acute  exacerbations  or  in  grave 
cases  is  attended  with  a  suspension  of  the  menstrual  function.  Graves' 
disease  is  rare  before  ])uberty  and  after  the  menopause. 

INFLUENCE  OF  PREGNANCY. 
Many  women  with  Graves'  disease  do  not  become  pregnant.    This  would 
seem  to  prove  that  a  normal  ovum  and  a  normal  Graafian  follicle  are  not  pro- 
duced in  these  cases.    We  know  that  Graves'  disease  is  subject  to  exacerba- 
tions and  remissions.     Pregnancy  does  occur  and  in  some  cases  has  a  bene- 

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RAXSOHOFF  MEMORIAL  VOLUME 


ficial  effect  on  the  course  of  the  disease.  In  others  pregnancy  has  ;i  decid- 
edly bad  effect.  In  api)arently  cured  cases  pregnancy  can  bring  on  an  acute 
attack.  I'his  (XTradcxical  effect  of  pregnancy  on  Graves'  disease  may  be 
explained  by  the  fact  that  when  the  corpus  luteum  of  pregnancy  is  normally 
developed  there  is  an  improvement  in  the  symptoms  of  the  patient  and  when 
the  corpus  luteum  is  functionally  deficient  there  is  an  exacerbation  of  the 
symptoms.  We  would  like  to  explain  the  fact  that  some  patients  may  go 
through  one  pregnancy  without  any  difficulty  and  the  next  may  cause  very 
alarming  manifestations  of  hyperthyroidism,  on  this  basis  of  either  a  normal 
or  deficient  corpus  luteum  of  pregnancy.  On  the  same  groimds  we  would 
like  to  explain  the  exacerbations  and  remissions  ordinarily  seen  in  Graves' 
disease  when  untreated,  vie.  when  the  rupture  of  the  Graafian  follicle  is  fol- 
lowed by  the  development  of  a  normal  corpus  luteum,  the  sym]itoms  amelio- 
rate and  vice  versa. 

A  further  proof  of  the  inter-relation  of  the  corpus  luteum  and  the  thy- 
roid is  offered  perhaps  by  mild  cases  of  myxoedema  which  show  a  normal 
thyroid  activity  between  menstrual  periods  and  an  active  myxoedema  during 
the  menstrual  function.  This  would  seem  to  indicate  that  the  corpus  luteum 
exerted  an  inhibitory  effect  on  the  thyroid  in  these  cases  and  that  a  thyroid 
gland,  which  was  capable  of  performing  its  function  fairly  normally  during 
the  intermenstrual  period,  lost  its  ability  to  do  so  during  the  period  of  the 
greatest  activity  of  the  corpus  luteum.     (Hertoghe;  Medical  Record,  1914.) 

Moreover,  the  same  antagonistic  action  is  seen  in  absolute  Cretins  who 
never  arrive  at  the  stage  of  puberty.  In  addition  to  these  facts,  our  clin- 
ical experience  would  warrant  our  assertion  that  this  inter-relation  of  thy- 
roid and  corpus  luteum  resolves  itself  into  the  fact  that  the  specific  hormones 
excreted  by  the  corpus  luteum  exerts  an  inhibitory  effect  on  the  thyroid 
secretions  and  that  hyperthyroidism  is  an  expression  of  dysfunction  of  the 
corpus  luteum  in  the  female  and  perhaps,  although  we  have  not  had  much 
experience,  of  the  interstitial  glands  of  the  testicle  in  the  male.  This  view 
is  also  held  by  Claude  and  Gougerot,  who  call  Graves'  disease  a  hypo- 
ovarial  disease 

OBJECTION  TO  THE  THEORY. 
The  most  serious  objection  to  this  theory  is  that  we  rarely  see  a  typical 
Graves'  disease  symptoms  complex  following  the  removal  of  ovaries  or  tes- 
ticles. The  vast  majority  of  individuals,  however,  have  a  normal  endocrine 
system.  After  a  more  or  less  prolonged  period,  when  one  gland  is  dis- 
turbed or  diseased,  it  is  possible  for  other  glands  to  make  the  compensation. 
We  know,  for  instance,  that  after  castration  in  the  human  family  as  well  as 
in  animals,  and  during  pregnancy  for  instance,  there  is  marked  increase  in 
the  size  of  the  pituitary  gland  and  that  this  enlargement  means  an  increased 
function  by  means  of  which  the  endocrine  balance  is  restored  and  main- 
tained.    Ovaries  and  testicles  arc  removed  onlv  as  a  rule  when  thev  are 


HERMAN  H.  HOPPE 


diseased  and  when  their  function  has  been  perverted  for  a  long  time  and 
nature  has  had  ample  opportunity  to  establish  a  compensation  before  the 
operation.  It  is  only  perhaps  in  individuals  in  whom  this  balance  cannot  be 
established  for  some  reason,  that  a  dysfunction  of  the  interstitial  sex  glands 
is  followed  by  hyperthyroidism.  In  two  cases  at  least  the  use  of  the  anterior 
lobes  of  the  pituitary  gland  was  followed  by  relief  in  male  cases  of  Graves' 
disease,  and  Renon  and  Delille  saw  a  Graves'  disease  symptom  complex  dis- 
appear as  the  result  of  the  simultaneous  administration  of  pituitary  and 
ovarian  extract. 

It  is  essential  to  prove,  if  the  above  theory  is  correct,  that  the  symptoms 
of  Graves'  disease  are  due  to  an  excessive  secretion  based  upon  an  excessive 
function  of  the  gland  rather  than  to  a  toxic  secretion  and  that  the  manifes- 
tations of  Graves'  disease  are  due  to  increased  thyroid  activity. 

THYROTOXICOSIS  OR  HYPER-.^CT1VITY? 

There  have  always  been  two  theories  on  which  the  development  of  the 
symptoms  of  Graves'  disease  have  been  based,  viz.,  the  toxic  theory  and 
theory  of  excessiz'e  secretion.  The  toxic  theory  is  based  upon  the  assump- 
tion of  a  perverted  function  of  the  thyroid  gland.  This  theory  is  probably 
on  the  wane,  the  results  obtained  from  surgery  would  seem  to  lead  to  this 
conclusion  and  the  almost  universal  adoption  of  the  terms  hyperthyroidism 
and  hypothyroidism  would  seem  to  indicate  that  the  abnormal  activities  of 
the  thyroid  gland  are  due  to  either  an  excessive  or  a  deficient  secretion  of  the 
thyroid  tissue.  According  to  Felta  we  do  not  need  to  assume  a  perverted 
function  of  the  thyroid,  in  Graves'  disease,  that  poisoning  and  excessive 
secretion  are  synonymous  terms.  A  normal  secretion  poured  into  the  cir- 
culation in  excess  will  poison  the  body.  Felta  calls  our  attention  to  adrenalin 
jioisoning  as  a  fitting  example. 

The  .symptom  complex  of  Graves'  disease,  especially  the  serious  cases, 
undoubtedly  points  to  pluriglandular  disturbance.  But  we  need  not  assume 
that  we  have  therefore  a  pluriglandular  disease,  for  we  cannot  have  a  marked 
hyperfunction  of  any  one  of  the  endocrine  glands  without  disturbing  the 
finiction  of  most,  if  not  of  all  of  them.  The  theory  on  which  the  use  of 
cor])us  luteum  is  based  is  that  Graves'  disease  and  hyperthyroidism  are 
ef|uivalent  terms. 

THE  CORPUS  LUTEUM  TREATMENT  OF  HYPER-THYROIDISM. 
4.  I  have  been  using  the  corpus  luteum  now  for  six  years.  I  was 
impelled  to  try  it  at  first  on  a  very  acute  case  of  Graves'  disease  because  of 
the  presence  of  amenorrhoea  which  had  persisted  for  a  year.  This  patient 
had  had  prolonged  rest  and  the  us-ial  medicinal  remedies,  but  went  from 
bad  to  worse.  She  had  lost  sixty  pcunds  in  weight.  This  patient  made  a 
complete  recovery  and  has  remained  well  for  the  past  five  years.  Since 
my  last  report  in  1918,  I  have  treated  twenty-five  additional  cases  and  have 


RAXSOHOfF  MEMORIAL  VOLUME 


had  most  of  the  cases  reported  previously  under  observation  and  have  seen 
them  from  time  to  time.  None  of  these  tifty  cases  were  doubtful  cases.  In 
making  the  clinical  diagnosis  of  hyperthyroidism,  I  have  established  for 
myself  the  rule  that,  if  there  is  no  bruit  in  the  thyroid  gland.  I  do  not  make 
ihe  positive  diagnosis  of  hyperthyroidism  and  place  the  cases  in  a  doubtful 
catagory.  All  of  the  above  cases  were  diagnosed  as  positive  cases  on  the 
above  test.  One  of  the  cases  reported  in  1917,  has  died  of  influenza,  all  the 
others  are  doing  well  and  some  of  them  seem  to  have  established  a  normal 
balance  of  the  endocrine  glands  and  do  not  take  corpus  luteum.  The  others 
are  comfortable  when  they  take  corpus  luteum. 

I  have  had  no  cases  of  hyperthyroidism  operated  on  since  1917.  In  the 
last  group  of  twenty-five  cases  one  man  died  twenty-four  hours  after  I 
had  seen  him  in  consultation.  The  patient  had  had  hyperthyroidism  for 
years — was  in  an  acute  relapse  at  the  time  of  the  consultation  and  was 
sutferiug  from  and  died  of  acute  myocardial  disease  leading  to  cardiac  dila- 
tation. Three  or  four  of  these  cases  were  very  acute — one  had  lost  sixty 
pounds  and  the  other  seventy  pounds — both  of  these  latter  cases  have  made 
practically  a  complete  physiological  recovery  and  have  taken  up  their  former 
occupations.  Both  were  women.  Both  had  extreme  cardio-vascular  symp- 
toms, exophthalmos,  diarrhoea  and  rapid  emaciation.  One,  the  wife  of  a 
physician,  has  made  a  perfect  recovery;  the  other  has  still  some  exoph- 
thalmos, and  an  enlarged  thyroid,  but  insists  that  she  is  well  and  has  worked 
in  a  factory  for  the  past  year.  This  second  group  contains  a  surgical  case 
which  had  the  thyroid  removed,  but  still  presented  all  the  objective  signs  and 
subjective  distress  of  hyperthyroidism.  She  has  improved  under  the  treat- 
ment. Three  of  the  other  cases  are  very  much  improved,  all  of  them  are 
satisfied  and  relieved.  In  the  latter  group  of  cases  there  is  but  one  male  and 
lie  has  done  well  on  extract  of  pituitary  gland. 

DET.AILS  OF  TREATMEXT. 

The  most  notable  and  the  most  rapid  improvement  is  seen  on  part  of  the 
cardio-vascular  symptoms  and  general  nervous  manifestations.  The  pulse 
rate  drops  quickly,  the  general  subjective  symptoms  caused  by  the  circula- 
tory disturbances  subside,  the  loss  of  weight  stops,  digestion  and  appetite 
become  normal,  the  nutrition  improves  and  the  patient  takes  on  weight. 

While  I  look  upon  the  corpus  luteum  as  the  specific  agent  in  the  treatment 
of  Graves'  di.sease,  I  have  not  discontinued  the  symptomatic  treatment,  nor 
the  attention  to  hygiene  and  diet.  For  after  Graves'  disease  has  been  estab- 
li.shed.  we  see  signs  of  pluriglandular  disturbance.  The  digestive  disturb- 
ances, the  increased  metabolism  and  the  rapid  emaciation  all  demand  symp- 
lomatic  treatment.  On  account  of  the  general  nervous  and  mental  irrita- 
bility, cases  of  Graves'  disease  are  not  very  easily  managed,  nor  are  they  as 
a  rule  faithful  to  the  treatment.  I  give  careful  attention  to  the  diet,  allow 
very  little  i)hysical  exercise  and  i)rescribe  much  bed  rest.     Quinine  hydro- 

Paije    >m 


HERMAN  H.  HOPPE 


hroniate  and  extract  of  belladonna  are  of  great  value.  I  usually  give  rwo 
grains  of  corpus  extract,  three  grains  of  hydrobromate  of  quinine  and  one- 
tenth  grain  of  the  extract  of  belladonna  after  each  meal.  After  the  cases 
show  improvement,  I  diminish  the  dose  to  two  per  day  and  even  when  the 
patients  are  apparently  well,  I  still  give  one  dose  per  day,  usually  at  bedtime. 
.'\.s  in  my  previous  report,  I  still  find  that  patients  who  take  tlie  treatment 
irregularly  or  who  discontinue  the  treatment  show  a  tendency  to  relapse  and 
to  have  an  exacerbation  of  all  symptoms.  We  believe  that  the  exacerbations 
and  remissions  which  are  ordinarly  seen  in  Graves'  disease  are  due  to  the 
fact  that  defective  ovaries  may  occasionally  produce  even  several  months  in 
succession  normal  corpus  luteum,  and  during  these  periods  show  an  improve- 
ment. We  believe  that  in  the  cases  which  have  recovered,  the  use  of  the 
corpus  luteum  has  tided  the  patient  over  and  assisted  the  patient  in  estab- 
lishing a  compensatory  secretion  by  one  of  the  other  endocrine  glands  and 
thereby  bringing  about  once  more  an  endocrine  balance  with  a  permanent 
relief  of  all  the  symptoms. 

CONCLUSION. 

The  theory  on  wliich  the  above  treatment  is  based,  therefore,  is  that 
hy])erthyroidism  is  caused  by  a  defective  secretion  of  the  interstitial  sex 
glands ;  that  the  hormones  of  the  interstitial  sex  glands  have  an  inhibitory 
and  regulatory  action  on  the  secretion  of  the  thyroid;  that  when  the  function 
of  these  interstitial  glands  is  deficient,  there  is  a  lack  of  physiological  inhibi- 
tion of  the  thyroid,  with  an  excessive  secretion  and  therefore,  hyperthyroid- 
ism. In  other  words,  hyperthyroidism  and  hypo-ovarianism  are  synonymous 
conditions. 

As  I  have  said  before,  the  mere  administration  of  corpus  luteum  alone 
will  not  relieve  these  cases.  Even  a  superficial  knowledge  of  Graves'  disease 
would  disabuse  our  minds  of  this  idea.  The  cases  require  careful  dietetic, 
hygienic  and  symptomatic  treatment.  r)Ut  whereas  my  previous  experience 
has  been  that  most  cases  with  the  above  symptomatic  treatment  combined 
with  quinine  hydrobromate  and  extract  of  belladonna  showed  but  inditifercnl 
results,  the  use  of  corpus  luteum.  in  conjunction  witli  this  general  treatment, 
gave  most  satisfactory  results. 

The  treatment  of  hyperthyroidism  with  corpus  luteum  is  comjiarable 
with  the  treatment  of  myxcedema  with  thyroid  extract.  As  long  as  we 
administer  thyroid  extract,  cases  of  myxoedema  and  hyperthyroidism  do  very 
well.  Rut  the  administration  of  thyroid  extract  will  not  make  a  defective 
thyroid  resume  a  normal  function.  Xor  will  the  administration  of  corpus 
luteum  cause  a  deficient  ovary  to  produce  a  mature  Graafian  follicle.  But  it 
has  been  my  experience  that,  as  long  as  we  administer  corpus  luteum  in 
Graves'  disease  or  in  its  period  of  exacerbation,  the  patient  is  improved  and 
can  be  kept  in  a  fairly  normal  condition. 


I.     THE  X-RAY  EXAMINATION   OF  THE   MASTOID    REGION* 

By  Samukl  Iglaueu.  B.  S.,  M.  D. 

Cincinnati. 

Ill  many  branches  of  medicine  and  surgery  the  Roentgen  rays  have  be- 
come almost  indispensable  as  an  aid  to  diagnosis,  and  frequently  the  nature 
of  some  obscure  condition  is  absolutely  determined  by  the  radiogram.  The 
value  of  radiography  has  become  well  established  in  the  field  of  rhinology, 
especially  in  the  examination  of  the  accessory  cavities  of  the  nose,  so  that 
sinusitis,  or  tumors  of  the  antrum  of  Highmore,  of  the  ethmoids,  and  the 
frontal  sinus,  can  be  definitely  outlined.  Radiography  in  rhinology  not  only 
lays  bare  pathologic  conditions,  but  also  gives  valuable  aid  in  outlining  anat- 
omic relations,  so  that  the  surgeon  may  proceed  with  greater  assurance  in 
opening  these  cavities  when  they  are  diseased.  Thus  Beck,^  after  obtaining 
an  exact  outline  of  the  frontal  sinus  in  the  skiagram,  turns  down  the  anterior 
wall  of  the  sinus  and  subsequently  replaces  it  by  a  plastic  operation.  Ingalls- 
(loes  not  hesitate  to  drill  into  this  cavity  by  the  nasal  route,  after  he  has 
determined  its  anatomic  position  in  the  radiogram.  To  Caldwell'  belongs 
(he  credit  of  having  established  the  projier  angle  for  the  delineation  of  both 
frontal  sinuses  upon  the  same  plate. 

In  exposing  the  temporal  bone  to  radiographic  examination,  greater 
obstacles  are  to  be  met  with  than  in  examining  the  sinuses  and  bones  of  the 
face,  because  it  is  difficult  to  obtain  a  profile  of  one  temporal  bone  without 
superimposing  upon  it  the  shadow  of  the  other.  In  fact,  the  chief  difficulty 
in  radiography  of  the  cranium  is  to  establish  the  proper  angle  at  which  the 
picture  is  to  be  taken,  in  order  to  ;ivoid  the  shadows  of  tlie  thicker  portion 
of  the  skull. 

Thus  \'oss''  and  Winckler,"'  b)-  taking  pictures  in  the  transverse  diameter 
of  the  skull,  report  excellent  results  in  outlining  the  mastoid  region  as  well 
as  determining  its  condition  of  health  or  disease. 

Kuhne"  and  Plagemann'  prefer  taking  pictures  in  the  occipito-frontal 
direction,  since  thereby  an  image  of  both  mastoid  processes  is  obtained  at  one 
time  and  upon  the  same  plate.  Judging  from  the  illustrations  accompany- 
ing their  article  this  method  is  open  to  objection,  since  the  temporal  bone 
is  too  far  removed  from  the  plate  to  give  a  sharp  image,  and  only  a  portion 
of  the  mastoid  process  appears  in  the  Roentgen  picture. 

Considering  the  difficulties  frequently  encountered  in  diagnosticating  dis- 
eases of  the  mastoid  process,  it  has  for  some  time  past  seemed  advisable  to 
me  to  obtain  radiograms  of  the  mastoid  region,  and  I  was  fortunate  in  having 
an  expert  radiologist.  Dr.  S.  Lange,  kind  enough  to  undertake  this  work. 
To  him  I  am  indebted  not  only  for  his  untiring  etiforts,  but  also  for  valuable 
suggestions. 

•Thesis  presented  to  the  .American  l.aryngolo^ical.  lihinolo^ical  and  OloIoKie.-il  Soeicty,  Janu- 
ary  1,   1909.      Keiirinldl  from  Annals  of  Olulogy,   Rhinology  and   Laryngology,   Ueiemher,   1909. 

Paijc  mi 


SAMUEL  IGLAUER 


The  greatest  obstacle  to  be  overcome  was  in  establishing  the  proper  angle 
from  which  uniform  resuUs  might  be  expected.  At  my  suggestion  the 
obHque  profile  of  the  temporal  region  was  employed.  Subsequently  Dr. 
Lange  suggested  taking  measurements  of  the  angle  of  inclination  of  the 
X-ray  diaphragm,  so  that  greater  precision  might  be  liad.  These  points  will 
be  further  elucidated  in  describing  the  technic. 

We  have  taken  radiograms  of  the  dry  skull,  of  the  cadaver  and  of  a 
considerable  number  of  patients.     In  all  \vc  have  collected  about  fifty  plates. 


I 

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M 

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i 

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Jb 

Radiography  of  Mastoid  Region,  showing  relative  positions  of  plate,  X-ray  dia- 
phragm and  patient's  head.  Note  the  inclination  of  the  X-ray  diaphragm.  (The 
radiograms  may  be  taken  to  advantage  with  the  patient  lying  on  his  side,  but  with  the 
diaphragm  in  the  same  relative  position  as  in  Fig.  I. 

Page  m.l 


RAXSOHOFF  MFMORL-iL  VOLUME 


of  the  mastoid  process 
For  the  same  reason  a 
..     The  auricle  is  then 


TECHXIC. 
'I'he  technic  is  as  follows  : 

A  small  piece  of  lead  foil  is  plastered  to  the  tij 
ill  order  to  fix  this  point  in  the  Roentgen  picture, 
coil  of  wire  is  introduced  into  the  auditory  meati 
drawn  forward  and  fastened  by  adhesive  plaster  to  the  cheek  of  the  patient 
in  order  to  hold  it  away  from  the  mastoid  region.  The  patient  then  lies  on 
his  side  on  the  table,  or  sits  upon  a  chair,  with  the  ear  to  be  examined  in 
contact  with  the  photographic  plate.  The  diaphragm  of  the  X-ray  tube  is 
then  adjusted  immediately  below  the  parietal  eminence  on  the  opposite  side 
of  the  patient's  head,  and  is  given  a  slant,  so  that  the  rays  will  be  directed 
through  the  cranium  toward  the  sigmoid  sinus  and  mastoid  process  of  the 
car  which  is  being  radiographed.  (  See  Figs.  1  and  3.)  In  this  position, 
the  temporal  bone  on  the  upper  side  of  the  skull  is  left  almost  entirely  out 
of  the  radiographic  field.  Dr.  Lange  has  measured  the  angle  of  inclinalioii 
of  the  axis  of  the  diaphragm  and  finds  it  to  be  as  follows: 


FIGURE  11. 

.  Quarter  section  of  a  skull  with  lead  foil  in  the  sinus,  and  a  wire  in  the  auditory 
meatus  and  in  the  middle  fossa.  (P  F)  Posterior  fossa.  (E)  Foramen  for  emissary 
vein.  (Arrow)  Indicates  descending  portion  of  facial  canal.  (O)  Orbit.  (Z)  Zygoma. 
Page  20  i 


SAMUEL  IGLAUER 


First,  it  is  inclined  25  degrees  to  the  basal  plane  of  the  skull,  and  sec- 
ondly, it  is  tilted  backward  20  degrees  from  the  coronal  plane  of  the  skull. 
(See  Fig.  1.)  This  step  of  the  technic  is  very  important  because  it  assures 
uniform  results. 

The  lime  of  exposure  \aries  from  20  to  50  seconds  with  an  electrolytic 
interrupter,  to  four  minutes  with  a  mercury  turbine  interrupter.  For  com- 
parison it  is  advisable  to  radiograph  both  temporal  bones  at  the  same  sitting. 

Figure  2  shows  a  quarter  section  of  the  dry  skull,  in  which  some  of  the 
landmarks  are  brought  out  by  filling  them  with  lead  foil.  This  experiment 
enables  the  observer  to  fix  the  anatomic  relations  in  subsequent  pictures. 
'I'his  radiogram  shows  very  well  the  internal  structure  and  relations  of  the 
temporal  bones  and  requires  no  further  description. 

The  next  illustration  (Fig.  3)  shows  the  mastoid  region  traced  from  a 
radiogram  taken  through  the  entire  skull.     The  anatomic  structures  are  here 


FIGURE 


Radiogram  of  a  dry  skull,  showing  left  mastoid  region  taken  in  an  oblique  profile. 
The  lower  shadow  (X)  is  the  right  mastoid  thrown  out  of  the  field  by  the  oblique 
direction  of  the  X-rays.  (M)  Meatus.  (T)  Tegmen,  (S  S)  Sinus.  (P)  Styloid 
process.  (Arrow)  Facial  canal,  in  the  mastoid.  (Z)  Zygoma.  (O)  Orbit.  (B  I  Floor 
of  post-fossa. 

Page  _"/.; 


RAXSOHOFF  MEMORIAL  VOLUME 


Print   and   tracing   from   plate   of   a   normal    mastoid    region    in   a   voung   woman. 
(*)   Meatus.     (X)   Mastoid  cells.     fS  S)   Sinus.     (M^   Mandible.     (E)'  Middle  fossa. 


FIGURE  V. 

Tracing  from  a  radiogram  of  a  normal,  left  mastoid  in  a  man  of  i7 .     (*)   Meatus. 
(T)  Large  cell  in  the  mastoid  tip.     (F)  Middle  fossa.     (S)  Sinus  (?).     (L  L)  Suture 
lines.     (M)   Mandible.     (O)   Orbit. 
Paai-  nii; 


SAMUEL  IGLAUER 


very  distinct,  and  it  will  be  observed  that  the  one  mastoid  is  entirely  out  of 
the  field. 

Figures  4  and  5  are  tracings  from  radiograms  of  norma!  mastnid  regions 
in  different  patients.  It  is  impossible  to  re])roduce  some  of  these  plates 
except  by  tracings.  These  illustrations  show  the  relative  position  of  the 
middle  fossa  of  the  skull,  the  outline  and  cellular  arrangement  of  the  mas- 
toid process,  the  position  of  the  external  auditory  canal  and  frequently  of 
the  sigmoid  sinus. 

As  may  be  judged  from  the  illustrations,  practically  all  of  the  skiagrams 
delineate  very  accurately  the  anatomic  relations  of  the  mastoid  process. 
Considering  the  great  variability  in  the  structure  of  the  temporal  bone,  it  is 
apparent  how  valuable  this  knowledge  obtained  prior  to  an  operation  may 
become.  Indeed,  should  radiography  give  no  further  information  than  this, 
it  would  still  repay  the  otologist  to  obtain  those  Roentgen  pictures.  As  a 
matter  of  fact,  however,  the  skiagrams  reveal  not  only  anatomic  relations, 
but  also,  in  some  cases,  pathologic  process  in  the  interior  of  the  mastoid 
process. 

In  certain  cases  of  chronic  suppurative  otitis  media  the  radiograms 
showed  practically  an  absence  of  mastoid  cells,  the  sclerosed  bone  throwing 
a  den.se  shadow.  Such  pictures  were  obtained  in  five  cases.  (See  Figs.  G 
and  7.)  In  four  instances  the  Roentgen  pictures  were  confirmed  by  oper- 
ation. 

In  one  case,  that  of  a  man  21  years,  with  chronic  otorrhea,  osteosclerosis 
was  diagnosticated  in  the  right  ear,  with  the  probable  absence  of  mastoid 
cells.  (Fig.  7.)  The  left  ear  taken  at  the  same  time  for  comparison, 
showed  a  massively  developed  pneumatic  process.  Operation  revealed  a 
dense  mastoid  process  with  a  very  small  antrum,  which  was  only  uncovered 
after  working  according  to  the  method  of  Stacke. 

A  second  operative  case  was  that  of  a  boy  of  twelve,  with  chronic  sup- 
puration in  the  left  ear.  The  sinus,  the  tegmen  tympani  and  the  mastoid 
process  were  found  exactly  in  the  condition  indicated  by  the  picture. 
(Fig.  8.) 

The  third  case  was  one  of  tuberculosis  of  the  middle  ear  in  a  man  of 
forty-five.  The  two  radiograms,  taken  at  intervals  before  the  operation, 
showed  a  very  large  mastoid  process  of  pneumatic  type  with  hazy  outlines 
of  its  cells.  Operation  revealed  a  large  mastoid  process  with  numerous  large 
cells,  most  of  which  were  filled  with  a  clear  serous  fluid.  The  middle  ear 
and  antrum  contained  granulations.     (Fig.  9.) 

The  fourth  case  was  operated  upon  too  recently  for  description. 

From  the  experience  gained  by  this  investigation,  the  following  conclu- 
sions may  be  drawn : 

First.    It  is  quite  feasible  to  radiograph  the  mastoid  region. 

Second.  The  best  skiagrams  are  obtained  by  directing  the  rays  so  as  to 
give  a  slightly  oblique  profile  of  the  temporal  region. 


RAXSOIIOFf  MliMORlAL  lOLUME 


FIGURE 


Tracing  from  a  radiogram.  Right  mastoid  region  in  a  case  of  chronic  otorrhea 
)f  many  years'  standing.  Note  absence  of  mastoid  cells,  t.  c,  osteosclerosis.  (S)  For- 
vard-lying  sinus.  (M)  Mastoid.  ^A)  Meatus.  (T)  Tegmen.  (R)  .■\scending  ramus 
.f  mandible.     (Patient  of  Dr.  William  Mithoefer.) 


(Case  !.■)  I-.  K.  Right  n\ast(iid  region,  .showing:  (P  P)  Osteosclerosis  of 
mastoid.  (S  S)  Sigmoid  sinus.  (M)  Mandible.  (M  F)  Middle  fossa.  (C)  Meatus. 
(Confirmed  by  operation.) 


SAMUEL  IGLAUER 


(Case  II.)  Tracing  from  a  radiogram.  Left  mastoid  region.  (M)  Meatus. 
(M  F)  Middle  fossa.  (C  C)  Mastoid  cells.  (S)  Anterior  border  of  sinus.  (J)  Man- 
dible.    (L  L)   Suture  lines.     (O)   Orbit.     (X)    Top  of  mastoid. 


FIGURE  IX. 

(Case   III.)      Radiogram  tracing  tuberculosis  of  middle  ear  and  mastoid.     Large 

mastoid   of    pneumatic   type.      Cells   appear    hazy   in  the    radiogram.      (Confirmed    by 

operation.)     (*)   Meatus.     (S)  Zygoma.     (O)  Orbit.  (M  F)   Middle  fossa.     ( I)   Man- 
dible. 


RAXS'OJIOff  MEMORIAL  I'OLUMIl 


Third.  The  radiogram  distinctly  outlines  the  anatomic  relations  of  the 
external  auditory  meatus,  the  limits  of  the  mastoid  process  and  of  the  mas- 
toid cells.  The  floor  of  the  middle  fossa  of  the  skull  is  shown,  as  well  as 
the  thickness  of  the  tegmen  tympani.  The  sigmoid  sinus  is  frequently 
delineated  and  its  position  indicated. 

Fourth.  Osteosclerosis  of  the  mastoid  bone,  following  prolonged 
otorrhea,  may  in  some  cases  be  determined  by  the  X-ray  examination. 

Fifth.  It  is  possible  that  pus  and  granulations  (\'oss).  as  well  as  seques- 
tra (Winckler),  in  the  mastoid  process  can  be  diagnosticated  by  means  of 
the  X-ray.  It  must  be  stated,  however,  that  acute  inflammation  of  the 
mucosa  is  difficult  to  differentiate  from  softening  of  the  bone  (  Plagemann). 

Sixth.  In  general  it  may  be  stated  that  radiography  should  prove  of 
great  value  in  the  determination  of  both  the  anatomic  and  pathologic  condi- 
tions within  the  temporal  bone. 

niBLIOGR.NPHV. 

1.  Jos.   Beck.     Jour.  Am.  Med.  Assoc..  August  8.   190«. 

2.  E.   Fletcher  Ingals.     Jour.   Amer.   Med.    Assoc.   May   9.    1908. 

3.  E.   W.   Caldwell.      Amer.   Quar.   of   Roentgenology,  January,    1907. 

4.  O.  Vos.  Verhand.  der  Deutsch.  Otologischen  Gesellschaft,  May.  1907.  Reprint  puli.  by 
Gustav  Fischer  in  Jena.  Also  Ref.  Zeitschrift  f.  Orenheilkunde.  Ed.  LI\'.  Heft  J.  p.  208.  Jiilv. 
1907. 

5.  Winckler.     Zeitschrift  f.   Ohrenheilkunde.     Bd.  LIV.      Heft   2.   p.  209,  July   I,    1907. 

6.  Kuhne  and  PlaRemann.  Fortschritte  auf  dem  Gebiete  der  Roentgenstrahlen.  Bd.  .XII. 
Heft  5.  September   1.   1908. 

7.  Plagemann.     Verhand,  der  Deutsch.      Roentgcn-Gescllscliaft.      IJd.   \\.      September,    19U8. 


THE  CLINICAL  VALUE  oF  RADIOGRAPHY  OF  THE  MASTOID 
REGION.* 

SAMUEL    ICLAUKK.    U.S.,    M  .D. 
Cincinnati. 

The  difficulties  encountered  in  radiographing  the  temporal  bone  are  due 
to  its  position  at  the  base  of  the  skull,  to  the  thickness  of  the  parts  that  thi- 
Roentgen  rays  must  penetrate,  and  to  the  liability  of  superimposing  the 
shadows  of  other  portions  of  the  skull  on  the  skiagram  of  the  temporal  bone. 
By  directing  the  rays  in  the  anteroposterior  (posteroanterior)  axis  of  the 
skull  Kuhne  and  Plagemann'-  ^  have  taken  radiograms  of  the  projecting  por- 
tions of  both  mastoid  processes,  and  have  drawn  clinical  deductions  there- 
from. Voss^  and  Winckler*  have  obtained  more  detailed  Roentgen  pictures 
of  the  temporal  bone  by  directing  the  rays  in  the  transverse  diameter  of  the 
skull. 

During  the  past  year  Dr.  S.  Lange,  radiologist  to  the  Cincinnati  Hos- 
pital, to  whom  I  am  greatly  indebted,  has  been  kind  enough  to  undertake  the 
radiography  of  the  mastoid  region  for  me.  After  some  experimentation, 
at  my  suggestion,  the  radiograms  were  taken  in  an  oblique  profile,  i.  e.,  the 
rays  coming  from  the  target  were  made  to  center  just  below  the  parietal 
eminence  on  one  side  of  the  skull  and  vvere  directed  through  the  cranium 
in  the  direction  of  the  temporal  bone  on  the  opposite  side  of  the  skull.  At  this 
angle  the  best  skiagrams  were  obtained.  In  this  position  Dr.  Lange  found 
that  the  axis  of  the  X-ray  diaphragm  was  tilted  upward  at  an  agle  of  25  de- 
grees from  the  base  of  the  skull  (Reid's  line),  and  that  it  was  inclined  back- 
ward 20  degrees,  from  the  vertical  plane  passing  through  both  external 
auditory  canals.  Figure  1  illustrates  this  double  inclination.  In  a  previous 
paper  on  this  subject^  I  have  given  further  details  concerning  the  technic, 
and  these  need  not  be  repeated  here. 

RADIOGRAPHY  OF  THE  NORMAL  MASTOID  REGION. 

In  the  normal  subject ;  skiagrams  obtained  by  this  method  delineate  the 
following:  (1)  The  mastoid  process  with  its  cells;  (2)  the  position  of  the 
external  auditory  meatus ;  (3)  the  line  marking  the  floor  of  the  middle  fossa  ; 
(4)  frequently  the  position  of  the  groove  for  the  sigmoid  sinus. 

Many  plates  in  addition  show  the  floor  of  the  posterior  fossa,  the  as- 
cending ramus  of  the  mandible  and  the  suture  lines  radiating  from  the 
asterion.    Figures  2  and  3  show  all  the  landmarks  above  mentioned.     From 

•Read  in  the  Section  on  I^aryngology  and  Otology  of  the  .\merican  Medical  .Association,  at  the 
Sixtieth  Anniial   Session,  held  at  Atlantic  City,  June.   1909. 

1.  Kuhne  and  Plagemann:     Fortschr.  a.  d.  Ceb.  d.  Roentgenstr..   Sept.   1,   1908.  xii,  No.    1 

2.  Plagemann:      Verhandl.   d.    Dcutsch.    Roentgen-Gesellsch.,    Sept..    1908,   iv. 

3.  Vos.  O.:  Verhandl.  d.  Deutsch.  Otol.  Gesellsch..  Mav.  1907;  reprint  pub  by  Gustav 
Fischer  in  .Tena;  also  abstr.  in  Ztschr.  f.  Ohrenh.,  July,   1907,  liv.  208. 

4.  Winckler:     Abstr.  Ztsch.  f.  Ohrenh..  July,   1907,  liv,  209. 


RAXSOIIOFF  MEMORIAL  VOLUME 


Fig.  1.  The  arrow  indicates  the  inclination  at  which  tlie  radiogram  sliould  be 
taken,  i.  e.,  the  X-ray  diaphragm  should  be  tilted  backward  20  degrees  from  the  ver- 
tical plane,  arid  should  be  inclined  upward  25  degrees  from  the  horizontal  plane.  (  .\s 
measured  by  Dr.  S.  Lange.) 

these  and  similar  ])lates  it  will  be  apparent  that  the  internal  anatomy  of  tht 
temporal  bone  may  readily  be  determined  by  radiography.  Considering  the 
great  variability  in  the  structures  of  this  bone,  the  knowledge  so  obtained 
prior  to  operation  will  prove  of  great  value  to  the  surgeon. 

R.\D10GRAPHY  OF  THE  PATHOLOGIC   MASTOID  REGION. 
Among   the    pathologic    cases    examined    were    seven    cases    of    chronic 
otorrhea,  one  subacute  case  and  four  acute  cases. 

-  In  cases  of  suppuration  of  long  standing,  attended  with  osteosclerosis  an(i 
obliteration  of  the  mastoid  cells,  the  dense  bone  shows  very  distinctly,  and 
the  sigmoid  groove  very  often  stands  out  sharply  in  the  picture.  The  posi- 
tion of  the  antrum  may  be  indicated  if  the  overlying  bone  is  not  too  dense. 


Fig.  2.  Radiogram  of  mastoid  region  of  a  skull:  (*)  .Auditory  meatus;  (M  F) 
middle  fossa;  (L)  lead  foil  in  middle  fossa;  (C)  large  cell  at  the  mastoid  tip;  {C ) 
small  cell;  (S  S)  sinus  ^marked  by  wires)  ;  (B)  jugular  bulb;  (P  F)  posterior  fossa; 
(O)  orbit;  (XX)  suture. 

Paiji-  ^1.1       ■ 


SAMUEL  IGLAIJER 


Seven  of  the  cases  which  had  been  radiographed  came  to  operation  and  the 
X-ray  findings  were  in  a  great  degree  confirmed.  It  may  be  interesting  to 
recount  these  cases  somewhat  in  detail. 


R.ADIOGRAMS  CONTROLLED  BY  OPERATION'. 

Case  \.  L.  K.,  male,  aged  21.  Diagnosis:  Chronic  suppurative  otitis  media  on 
the  right  (of  uncertain  duration).  X-ray  examination  showed  a  dense  shadow  over 
the  right  mastoid  region,  with  the  absence  of  cellular  structure.  The  position  of  the 
sinus  is  indicated.  The  left  normal  mastoid  region  showed  an  enormously  developed 
pneumatic  process.     Operation,  August  28,  1908,  confirmed  the  findings  in  the  right  ear. 


Fig.  3.  Tracing  from  radiogram.  Normal.  Mastoid  region  of  a  child.  (M  F) 
Middle  fossa;  (C  C)  mastoid  cells:  (S  S)  sigmoid  sinus:  (J)  jaw;  (Z)  zygoma; 
(  P  F)  posterior  fossa. 

Remarks. — In  this  case  it  seems  likely  that  the  chronic  suppuration  retarded  the 
development  of  the  right  mastoid 

Case  2.  M.  S.,  male,  aged  12.  Diagnosis:  Chronic  suppurative  otitis  media,  right 
and  left,  of  seven  years'  standing.  X-ray  examination  showed  a  diploetic  mastoid,  a 
high  tegmen,  and  the  line  marking  the  position  of  the  sinus.  .\  meatomastoid  operation 
(November  21,  1908)   showed  the  anatomic  relations  as  in  the  radiogram. 

Remarks. — The  tip  was  not  disturbed  because  it  appeared  normal  in  the  radio- 
gram. In  the  light  of  subsequent  experience,  the  radiogram  in  this  case  would  have 
indicated  that  operation  might  have  been  deferred. 

Case  3.  A.  Z.,  male,  aged  55.  Diagnosis  :  Subacute  tuberculosis  of  left  middle 
ear  and  mastoid.  X-ray  examination  (two  plates  at  different  times)  of  left  ear  only, 
showed  a  very  large  pneumatic  mastoid  with  hazy  outlines  of  its  cells.  Radical  opera- 
tion revealed  pus  and  granulations  in  the  middle  ear  and  antrum,  and  showed  serum  in 
the  mastoid  cells,  some  of  which  extended  behind  the  sinus. 


Fig  4.  Tracing  from  a  radiogram  showing  osteosclerosis  of  mastoid  (left)  and  a 
defect  (?)  ini  tegmen  antri.  (M)  Sclerosed  mastoid;  (M  F)  middle  fossa:  (D)  de- 
fect;  (C)  external  auditory  meatus;   (J)  mandible. 


RAXSOHOFF  MEMORIAL  VOLUME 


Fig.  5.  Radiogram  tracing  of  left  mastoid  region,  showing  osteosclerosis  of  mas- 
toid process*.  (M)  Middle  ear;  (M  F)  middle  fossa;  (S  S)  sigmoid  groove:  (L  L) 
suture  lines. 


Remarks. — Some  of  these  cells  might  have  been  overlooked  had  they  not  been 
delineated  in  the  radiogram. 

Case  4.  H.  X.,  male,  aged  62.  Diagnosis:  Chronic  suppurative  otitis  media  in 
left  ear  with  caries  of  the  promontory:  unhealed  radical  mastoid  in  the  right  ear. 
Radiogram  (Fig.  4)  of  left  mastoid  region  showed  dense  shadow  of  ostersclerosis,  and 
a  few  cells,  just  indicated,  in  the  antrum  region.  A  small  break  was  noted  in  the  line 
of  the  middle  fossa  and  a  tentative  diagnosis  of  a  defect  in  the  tegmen  antri  was  made. 
Radiogram  of  the  right  ear  showed  large  opening  made  by  a  previous  operation. 

Ol'eration. — December  29,  1908.  This  revealed  a  dense  sclerosed  mastoid,  large 
antrum  tilled  with  pus  and  granulations,  and  a  defect  in  the  tegmen  antri  with  the  dura 
covered  with  granulation  at  this  point. 

Subsequent  History. — The  patient  died  on  the  forty-first  day  after  the  operation. 
Postmortem  revealed  tuberculous  lesions  in  apices  of  both  lungs  and  a  tuberculous 
caries  of  the  right  internal  ear  and  pyramid.  The  temporal  bone,  showing  defect  over 
the  antrum,  was  removed. 


Fig.  6.  Tracing  from  a  radiogram.  Xormal  mastoid.  (M)  Meatus;  (M  F)  mid- 
dle fossa:  (S  S)  sinus;  (.C  C)  mastoid  cells:  (P  F)  posterior  fossa:  (L  L)  suture 
lines;  (J)  mandible;  (O)  orbit;  (Z)  zygoma.     (Right  mastoid  region  of  Case  5.) 

Case  5.  H.  B.,  female,  aged  4.  Diagnosis:  Chronic  mastoiditis  on  the  left:  right 
ear  normal.  X-ray  examination:  An  excellent  picture  of  the  left  side  showed  a 
dense  shadow  of  osteosclerosis  and  clear  zone  corresponding  to  the  middle  ear  and 
antrum,  the  sinus  being  sharply  outlined  (Fig  5).  The  right  mastoid  shows  normal 
diploetic  bone  and  the  sinus  (Fig.  6).  Operation  January  11,  1909,  showed  a  small 
fistula  in  the  external  auditory  meatus  leading  into  the  antrum,  which  was  filled  with 
granulations ;  the  sinus  was  not  uncovered. 

Remarks.— ThQTe  is  a  striking  contrast  between  the  radiograms  of  the  right  and 
left  mastoid  regions. 

Case  6.  F.  M.,  male,  aged  2Yi.  Diagnosis:  Acute  otitis  media  with  mastoiditis 
on  the  left.  X-ray  examination  of  the  right  side  showed  mastoid  process  of  infantile 
type.  The  left  shows  the  same  in  addition  to  the  outlining  of  the  posterior  semi- 
circular canal  (Fig.  7).  Operation  January  19,  1909,  revealed  softened  bone  about  the 
mastoid  antrura 

Page  ni 


SAMUEL  IGLAUER 


Fig.  7.  Left  mastoid  region,  showing  posterior  semicircular  canal :  (M)  Meatus; 
(D)  diploetic  bone;  (P  F)  posterior  fossa;  (O)  orbit. 

Remarks. — The  outlining  of  the  semicircular  canal  on  the  one  side  and  not  on  the 
other  would  indicate  that  the  bone  over  the  canal  was  softened. 

Case  7.  J.  R.,  male,  aged  21.  Diagnosis:  Chronic  suppuration  in  the  right  and 
left  ear  (of  years'  duration).  X-ray  examination  (Fig.  8)  of  the  right  ear  only  (two 
pictures)  showed  osteosclerosis,  absence  of  cells  from  the  tip  region  and  a  rather 
forward  lying  sinus.  The  meatomastoid  operation  (February  3,  1909)  uncovered  a 
small  deep-seated  antrum  with  a  few  adjacent  cells  containing  a  few  drops  of  pus; 
the  sinus  was  not  uncovered. 

Remarks. — The  tip  of  the  mastoid  was  not  disturbed,  since  the  skiagram  showed 
that  it  was  not  involved. 

Ill  addition  to  the  above,  live  patients  on  whom  ma.stoid  operation  had 
been  performed  were  radiographed  after  operation,  and  the  ;ippearance  of 


Fig.  8.  Tracing  from  radiogram:  (M)  Meatus;  (I)  antrum  (?)  ;  (M  F)  middle 
fossa;  (P)  sclerosed  mastoid  process;  (S)  sigmoid  groove;  (Z)  zygoma;  (J)  ascend- 
ing ramus  of  upper  jaw. 

the  operation  cavity  noted.  One  of  these  skiagrams  taken  several  months 
after  a  Schwartze  operation  was  especially  interesting,  since  it  showed  that 
a  number  of  cells  had  not  been  opened,  and  still  the  patient  had  made  a 
perfect  recovery. 

The  number  (four)  of  acute  cases  examined  is  too  limited  to  permit  of 
any  definite  conclusions  being  drawn.  One  of  these  came  to  operation  as 
already  described  above.  The  second  case,  that  of  a  little  girl  of  10,  simu- 
lated mastoiditis.  The  Roentgen  picture  of  the  affected  side  showed  a  hazi- 
ness of  the  mastoid  cells  with  clear  cells  on  the  sound  side.     The  patient  re- 


RAXSOHOPF  MEMORIAL  VOLUME 


covered  without  operation,  and  the  radiogram  taken  six  months  after  re- 
covery showed  that  the  cells  had  regained  their  normal  contour. 

The  third  case  of  acute  otitis  media  showed  similar  clouding  of  the  cells 
on  the  affected  side.  These  two  cases  are  interesting  as  confirming  the  con- 
tention of  V.  Troelsch*  and  of  Politzer,'  that  the  mastoid  process  is  involved 
in  most  severe  cases  of  acute  middle-ear  infection.  The  skiagram  in  the 
fourth  case,  which  is  too  recent  for  complete  description,  shows  a  fistula 
leading  into  a  large  abscess  cavity  in  the  mastoid  process.  It  appears  prob- 
able that  repeated  X-ray  examination  in  acute  cases  will  give  valuable  infor- 
mation concerning  the  progress  of  the  disease. 

CON'CLUSIOXS. 
]n  conclusion  it  may  be  stated: 

1.  The  most  satisfactory  Roentgen  pictures  may  be  obtained  in  oblique 
profile  of  the  temporal  bone. 

2.  The  internal  anatomy  of  the  temporal  bone  can  be  determined  prior 
to  operation,  and  the  knowledge  so  obtained  is  a  great  aid  to  the  surgeon. 

3.  Osteosclerosis  of  the  mastoid  secondary  to  chronic  suppuration  can 
usually  be  diagnosticated  by  radiography. 

4.  It  is  likely  that  defects  in  the  limits  of  the  temporal  hone  will  appear 
in  the  radiogram. 

5.  Cases  failing  to  heal  after  operation  should  be  controlled  by  skiag- 
raphy, as  this  may  reveal  the  seat  of  the  trouble. 

6.  The  value  of  the  Roentgen  examination  in  cases  of  acute  mastoiditis 
remains  to  be  determined. 

6.  Troelsch,   A.   von:      Lehrbuch   der   Ohrenheilkundc.   Lcipsic.    1881.   pp.    291-410. 

7.  Politzer,   A.:     Ohrenheilkunde.   89.1.  p.  417. 


THE   STRUCTURE   AND   MECHANICS   OF   DEVELOPING   CON- 
NECTIVE TISSUE.* 

Raphaf.i,  Isaacs. 

Cincinnati. 

When  the  fluid  part  of  blood  is  precipitated,  the  clot  of  fibrin  has  a  well- 
developed  structure  of  interlacing  fibrils.  The  production  of  this  definite 
.structure  from  a  fluid  suggests  that  fibrillar  appearances  elsewhere  in  the 
tissues  may  have  a  similar  origin.  Such  fibrillar  textures  are  seen  in  con- 
nective tissue,  in  basement  membranes,  in  cement  substance  between  cells, 
and  in  the  neurogliar  tissue  of  the  nervous  system.  The  present  paper  is  ?. 
study  of  these  structures  and  deals  with  the  growth,  consistency,  and  re- 
actions of  connective  tissue  and  cement  substance.  The  conclusions  point 
to  the  view  that  the  so-called  connective-tissue  fibrils  are  artifacts,  and  that 
the  cement  substance  and  basement  membranes  are  parts  of  a  homogeneou-: 
intercellular  jelly.  The  variation  in  precipitation  pattern  gives  a  histologi- 
cal basis  for  recognizing  diflferent  stages  in  the  physiology  of  organs. 

NOMENCLATURE. 

In  a  histological  section  of  "fixed"  connective  tissue,  fine  fibrils  can  he 
seen  stretching  between  the  cells  (Fig.  1).  These  are  called  connective- 
tissue  fibrils  (Mall,  '02)  or  cxoplasmic  fibrils  (Mall,  '02;  Flint.  '04)  or 
coUaginous  fibrillae  (Bell  '09).  In  the  central  nervous  system  a  somewhat 
similar  group  of  fibrils  are  known  as  neuroglia  fibrils  or  fibrillated  endoplasni 
( Hardesty,  '04).  The  name  white  or  collagen  fibers  is  given  to  a  group  of 
highly  refractive,  homogeneous  strands  of  tissue  found  in  skin  and  tendon, 
as  well  as  in  other  parts  of  organs.  The  yellow  or  elastic  fibers  are  also 
definite  large  threads  of  tissue,  found  in  many  organs.  This  paper  deals 
with  the  development  of  the  white  and  yellow  fibers,  and  also  the  intercellu- 
lar jelly,  a  homogeneous  substance  lying  between  the  cells  and  fibers,  and 
giving  rise,  according  to  this  view,  to  artificial  fibrils  on  fixation  or  dehydra- 
tion. 

MATERIALS  AND  METHODS. 

For  the  purpose  of  studying  the  structure  and  development  of  con- 
nective tissue,  chick,  ])ig,  and  human  embryonic  material  of  different  ages 
was  used,  the  fixation  and  staining  being  varied  to  study  the  effects  under 
various  conditions.  Living  tadpoles  and  embryos  of  the  chick  and  pig  and 
adult  frogs  were  used  for  the  study  of  fresh  tissue.  The  experiments  were 
conducted  along  two  lines.  The  nature  of  the  tissues  was  studied  from  the 
animal  tissue,  and  experiments  were  carried  out  with  colloid  solutions  of 
gelatin,  egg  albumin  and  fibrin,  of  known  strength  and  composition,  under 

•  From  the  Anatomical  Record.   December,   1919. 


RANSOM  OFF  MEMORIAL  VOLUME 


Fig.  1.     Appearance  of  connectiv. 
micrograph.     55-mm.  pig  embryo.     Bouin 
haemotoxvlin. 


rils  ami  fibrin  clot  in   vessels.     Photo- 
-Mallory's  connective-tissue  stain   and   iron 


controlled  laboratory  conditions.     The  technique  in  each  case 
the  discussion  of  the  phenomena  in  question. 


given  under 


I'.F.H.AVIOR  OF  CERTAIX  COLLOIDS. 
In  dealing  with  living  tissues,  we  are  studying  substances  in  a  colloid 
state.  Some  of  the  properties  of  protoplasm  are  properties  of  colloids.  AV'hen 
we  see  protoplasm  absorbing  water  or  secreting  it,  we  are  naturally  reminded 
of  a  similar  behavior  in  such  substances  as  gelatin,  fibrin,  or  white  of  egg. 
In  these  substances  we  can,  by  using  filtered  solutions,  free  them  from 
morphological  structures.  Yet  on  precipitation  we  can  produce  elaborate 
patterns  (Hardy,  '99:  Butschli,  '92)  (Fig.  2,  C).  These  substances,  when 
in  the  jelly  state,  can  give  rise  to  structures,  resembling  fibers  and  fibrils, 
if  they  are  put  under  pressure  or  stress.  A  gelatin  jelly,  on  pressure,  can  be 
broken  into  many  droplets  of  different  sizes,  which  give  rise  to  structures 
resembling  fibers  and  other  details  of  tissues.  These  structures  round  up 
into  drops  when  pressure  is  released.  The  behavior  of  fresh  connective 
tissue  is  much  the  same.     W'lien  compressed  between  cover-glasses  under 

Page  JIS 


RAPHAEL  ISAACS 


i0 


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e 


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^^.\ 


-?v  2  F 

Fig.  2.  Corresponding  areas  of  subcutaneous  connective-tissue  of  a  six-day  chick, 
fixed  with  various  sokitions  and  stained  with  Mallory's  connective-tissue  stain. 

A.  Connective  tissue  extract  fourteen-day  chick  (salt  solution),  filtered,  pre- 
cipitated with  Zenker's  solution  and  stained  with  Mallory's  connective-tissue  stain. 
Camera-lucida  drawing. 

B.  Fixed  in  Bouin's  solution. 

C.  Egg  albumin,  filtered,  and  precipitated  with  Zenker's  solution.  Camera-lucida 
drawing. 

D.  Fixed  in  Zenker's  solution. 

E.  Fixed  in  Van  Gehuchten's  solution. 

F.  Fixed  in  absolute  alcohol.     Camera — lucida  drawings. 

the  niicroscope.  we  see  many  striicture.s,  but  release  of  pressure  results  in 
little  gelatinous  droplets  with  but  little  structure. 

Syneresis,  the  property  of  colloids,  which  give  rise  to  the  secretion  of  a 
fluid  containing  the  substance  of  the  colloid  in  a  dilute  state,  must  be  taken 
into  consideration  when  the  colloids  of  the  tissues  are  considered.  This 
process  takes  place  comparatively  quickly  when  viewed  under  the  misro- 
scope,  and  a  few  minutes  make  a  definite  change  in  the  consistency,  tough- 
ness, and  refraction  of  the  colloid  studied.  The  colloids  which  tend  to  under- 
go irreversible  changes,  as  white  of  egg,  show  this  property  to  a  marked 
degree,  and  the  differences  in  appearance  are  striking.  One  does  not  ap- 
preciate what  elaborate  structures  and  quick  changes  can  be  produced  in 
this  way  until  the  process  is  studied  under  a  high  magnification.  The 
structures  produced  can  be  emphasized  by  stains. 

Many  inorganic  salts,  when  precipitated  under  the  microscope,  present 
"patterns"  of  interlacing  fibrils,  composed  of  strings  of  minute  granules 
or  cyrstals.  Such  pictures  simulate  the  fibril  patterns  of  colloidal  proteins, 
and  remind  one  of  the  delicate  cytological  structures  often  shown  in  fixed 
tissue. 


Page   21 


RAXSOHOff  MEMORIAL  IXILUME 


THE  INTERCELLULAR  JELLY. 

The  jelly-like  nnture  of  young  embryos  is  a  matter  of  common  experience 
with  all  who  have  handled  young  chicks  or  pigs.  \Mien  lifted  up  by  any 
l^art,  they  elongate  and  tend  to  stretch.  They  have  the  consistency  of  thick 
mucus,  and  a  very  small  force  is  required  to  tear  oiT  a  part  or  cause  com- 
jiression  or  strain.  With  increase  of  age.  an  increase  of  firmness  is  noted. 
For  microscopical  examination  of  the  intercellular  substance  it  is  necessary 
to  put  small  pieces  in  a  hanging  drop  in  a  moist  chamber  or  underneath 
a  cover-glass  on  a  slide,  sealed  with  vaselin.  no  fluid  of  any  kind  being 
added.  The  temperature  can  be  kept  constant  and  evaporation  can  be 
avoided  to  a  certain  extent.  However,  the  pulling  and  squeezing  of  the 
tissue  in  handling  and  cutting  and  the  changes  of  tension  when  flattened 
against  the  cover-glass  are  factors  to  be  considered  in  interpreting  the  re- 
sults. Under  favorable  conditions,  observations  may  be  taken  on  the  tissue 
for  a  few  minutes  without  much  physical  change.  Maxinow  ('06,  p.  683) 
used  a  somewhat  similar  method,  but  at  this  technique  did  not  show  up 
certain  cellular  structures  which  he  had  expected,  he  emphasized  these 
structures  by  producing  a  local  oedema  with  physiological  salt  solution.  Th-? 
results  of  such  a  procedure,  however,  require  cautious  interpretation,  as  the 
equilibrium  of  the  intercellular  colloids  is  easily  disturbed,  a  process  often 
encountred  in  the  physiology  and  pathology  of  connective  tissue. 

The  subcutaneous  tissue  in  a  five-day  chick  reacts  as  a  mass  of  jelly 
when  touched.  The  tissue  can  be  indented  with  a  blunt  needle,  and  the  celh'. 
and  substances  around  the  point  are  bent.  If  a  piece  of  tissue  be  "fixed" 
in  this  position,  the  position  cells  will  show  the  results  of  the  pressure,  but 
the  "connective  tissue  fibrils"  will  radiate  in  all  directions,  independently 
of  the  lines  of  force  of  the  pressure.  If  they  had  been  present  in  the  living 
tissue,  one  would  expect  to  see  some  results  of  compression,  as  the  cells 
themselves  show.  In  the  living,  the  cells  and  the  substance  between  them 
act  as  if  they  were  a  mass  of  the  same  consistency  throughout,  and  the 
physiological  unit  for  response  to  pulls  and  tension  is  the  region  afifected,  not 
separate  cells. 

When  tissue  is  mounted  as  described,  it  becomes  flattened  against  the 
cover-glass,  and  a  narrow  zone  of  a  jelly-like  colloidal  substance,  containing 
granules,  forms  the  peripheral  region.  This  jelly  responds  to  a  touch  with 
a  needle,  much  as  does  the  tissue  itself.  On  indenting  one  side,  granules 
throughout  the  jelly  move  in  response  to  the  strain  set  up.  The  jelly  is 
probably  composed  of  intercellular  substance — ^"tissue  juice,"  lymph,  and 
plasma.  The  intercellular  colloid  is  more  viscous  than  lymph,  and  does  not 
run  up  into  a  capillary  tube,  as  does  the  latter. 

Varying  with  the  conditions,  this  jelly  undergoes  a  change  on  standing 
from  two  to  five  minutes.  The  granules  of  various  kinds  begin  to  aggluti- 
nate around  the  outer  edge  of  the  jelly  ring,  and  the  peripheral  zone  be- 
comes stiflfer.    A  process  re.sembling  crystallization  takes  place,  resulting  in 

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RAPHAEL  ISAACS 


the  formation  of  a  network  from  the  masses  of  granules.  The  netvvorl; 
is  microscopic,  and  under  low  ]50wer  resembles  a  fuzzy  mass  with  a  ground- 
glass  efifect.  The  basis  is  a  fine  matrix  of  fibrillae,  made  up  of  granules,  but 
sometimes  it  is  fairly  homogeneous.  It  resembles  connective-tissue  fibri!.^ 
in  appearance,  taking  the  same  stains — aniline  blue,  orange-G,  and  acid 
fuchsin.  The  behavior  is  similar  to  that  of  coagulating  fibrin.  Ranviev 
('89)  described  a  similar  process  as  the  normal  method  of  formation  of  the 
large  white  fibers  of  the  connective  tissues. 

This  process  may  be  hastened  by  drying,  heat,  dehydrating,  and  coagu- 
lating fixatives.  Formalin  gas  produces  a  fairly  homogeneous  fixation,  but 
dehydrating  destroys  this  efTect.  The  fibrils  formed  correspond  closely  to 
Baitsell's  ('15)  fibers,  formed  from  the  fibrin  clot  of  cultures  of  chick  tissue 
in  vitro.  He  points  out  that  "the  transformation  of  the  fibrin  net  results 
in  the  shrinkage  of  the  clot.  It  also  becomes  very  tough  and  resistant  to 
injury."  The  process  is  hastened  by  mechanical  manipulation  of  the  clot 
with  needles.  This  same  phenomenon  can  be  reproduced  in  filtered  egg  al- 
bumin, manipulation  giving  rise  to  the  appearance  of  well-defined  fibrils. 
The  intercellular  substance  clots  as  if  it  had  fibrin  as  its  basis,  but  the  varia- 
tion in  staining  and  the  consistency  during  life  give  the  impression  that  some 
mucoid  elements  are  present  in  addition.  The  jelly  is  more  viscid  than 
either  plasma  or  lymph,  and  does  not  run,  as  do  these  fluids,  but  it  can  be 
made  to  undergo  a  gradual  flowing.  This  holds  true  for  all  stages,  from  the 
embryonic  to  the  adult  tissue. 

As  the  peripheral  fibrils  form  in  our  preparations,  a  watery  fluid  ac- 
cumulates just  around  the  tissue  itself  and  in  the  meshes  of  the  fibrils.  Th^s 
process,  in  efifect,  is  analogous  to  that  of  syneresis  in  colloid  gels,  and  i^ 
familiar  to  us  in  the  liquid  accumulation  over  agar-agar  or  gelatin  jelly.  It 
takes  place  inde])endcntly  of  d.'ving  eft'ects  (Graham  in  M.  Fischer,  '15.  ]). 
240).  As  soon  as  this  dilute  liquid  forms,  the  cells  in  contact  with  it  swell, 
probably  due  to  the  increased  acid  content  as  the  tissue  dies  or  to  the  avail- 
ability of  "free"  water.  This  test,  accompanied  by  the  brighter  a])iiearanc>- 
of  the  nuclei,  which  in  the  perfectly  fresh  tissue  can  be  only  indistinctl\ 
located,  we  use  as  signs  of  the  beginning  of  the  death  process.  The  nucl'i 
appear  brighter,  either  because  they  undergo  a  change  of  consistency  and 
become  more  viscous  or  else  because  the  cytoplasm  becomes  less  dense,  due 
to  the  absorption  of  water.  When  the  term  fresh  tissue  is  used  in  thi; 
paper,  it  refers  to  the  condition  before  the  appearance  of  these  changes. 
The  blood  corpuscles  do  not  change  shape  for  some  time  after  this,  and  a|:- 
])ear  less  sensiti\e  than  the  embryonic  tissue  cells  in  this  respect.  However, 
as  the  changes  take  ])lace,  the  nuclei  of  the  erythrocytes  show  ver}'  clearl-,' 
in  the  chick  material.  The  fact  that  blood  plasma  is  relatively  more  dilute 
than  the  intercellular  colloids  proliably  accounts  for  this  difference  of  be- 
havior, and  this  factor  should  he  taken  into  account  in  interpreting  tissue 
cultures  in  which  plasma  is  used.  The  preservation  of  the  shajje  of  the 
blood  corpuscles  is  no  test  for  isotonicity  as  far  as  the  tissues  are  concerned. 

Page  ;.'.■/ 


R.-iXSOIWFP  MEMORIAL  VOLUME 


as  the  corpuscles  do  not  change  in  salt  solution  in  the  presence  of  "free" 
water  (not  in  colloid  combination).  The  tissue  cells  under  these  circum- 
stances are  affected  immediately. 

In  the  fresh  tissue  itself  (chick  and  pig  embryos)  the  position  of  the 
cells  can  be  made  out  fairly  accurately.  No  free-flowing  intercellular  "tissue 
lymph"  can  be  demonstrated.  On  tilting  a  slide  containing  a  tissue  mount, 
the  intercellular  substance  remains.  It  does  not  run  out  under  pressure, 
showing  that  most  of  the  liquid  is  held  in  colloid  combination.  Sutflcient 
pressure,  however,  easily  crushes  the  cells,  and  a  considerable  amount  of 
liquid  is  liberated  in  this  way.  This  liquid  flows  readily,  differing  from  the 
intercellular  colloid.  The  spaces,  corresponding  to  the  intercellular  con- 
nective-tissue spaces  of  fixed  tissue,  are  filled  with  a  clear,  homogeneous  jelly- 
like substance,  which,  in  the  younger  embryos,  has  the  consistency  ( not  nec- 
essarily concentration)  of  a  "wobbly"  gelatin  gel. 

The  phenomenon  of  compression  of  this  colloidal  material  is  very  in- 
structive, as  we  can  easily  reproduce  some  of  the  processes  taking  place  in 
the  developing  embryo.  A  needle  pushed  into  the  tissue  causes  a  response 
in  all  parts  of  the  tissue,  as  seen  by  the  movement  of  visible  granules.  It 
can  be  described  best  as  the  jarring  of  a  colloid  jelly.  Cuts  close  up  with 
but  little  evidence  of  separation,  and  the  pathway  of  a  needle  withdrawn  i^ 
apparently  obliterated.  If  a  piece  of  the  tissue  is  suspended  from  the  tip 
of  a  needle  or  forceps,  the  lower  end  rounds  up,  as  does  a  drop  of  stringy 
mucus.  If  a  freshly  cut  piece  of  tissue  is  placed  on  top  of  a  second  piece, 
and  the  two  are  killed  and  fixed  in  this  position,  with  no  other  pressure 
than  the  weight  of  the  tissue,  it  is  found  on  sectioning  that  fibrils  extend  in 
places,  without  interruption  from  piece  to  piece  (Fig.  3).  This  suggests 
that  the  fibrils  are  formed  by  the  dehydrating  or  coagulating  action  of  the 
fixatives  from  the  homogeneous  jelly.  If,  however,  the  bridging  fibrils 
were  merely  pre-existing  fibrils  of  one  piece  which  have  stuck  to  the  other 
piece,  then  we  would  expect  the  fibril  to  be  present  throughout  the  gap  be- 
tween the  pieces  of  tissue.  Fibrin  would  give  a  similar  picture.  The  fibrils 
are  present,  however,  only  in  places,  presumably  where  the  colloid  has  had 
time  to  ooze.  Of  course,  air  bubbles  must  be  excluded.  Fibrils  in  sections, 
then,  may  stretch  across  between  parts  which  in  the  living  may  have  been 
in  contact  or  separated  by  the  intercellular  jelly.  Sections  often  show  such 
pictures  around  the  more  solid  organs,  as  the  thyroid  or  thymus,  and  thev 
suggest  that  these  organs  evidently  push  into  the  connective  tissue,  which 
conforms  to  the  new,  irregular  outline,  by  a  flowing  or  oozing  process,  re- 
minding one  of  the  tissue  closing  in  on  the  pathway  of  a  withdrawn  needle. 

In  compressed  tissue,  which  is  fixed  and  sectioned,  the  cells  show  the 
result  of  the  pressure  by  their  alignment — usually  being  flattened  out,  with 
their  long  axis  perpendicular  to  the  direction  of  the  pressure — but  the  fibrils 
of  the  section  show  no  evidence  of  the  stress. 

In  living  tadpoles  Clark  ('12)  describes  a  delicate  network  of  minute 
tibrillae  between  the  cells.     These,  however,  are  not  as  numerous  as  the 


RAPHAEL  ISAACS 


Fig. 
killed   in 


])iecL'S   of   tissue,   which   have  heen  allowed   to   t 
position.      Photomicrograph.     Mallory   connecti\e-tissiie 


fibrils  which  the  fixed  tissue  show.  These  fibrils,  which  are  seen  in  the  living, 
can  l)e  picked  out  from  the  connective-tissue  fibrillae  after  the  section  \c, 
fixed,  and  suggest  the  branching  cytoplasmic  processes  of  stellate  cells. 

When  a  precipitating  agent,  as  mercuric  chloride,  acts  on  colloidal  solu- 
tions, as  of  egg  albumin,  of  different  strengths,  the  substance  is  precipitated 
in  greater  bulk  from  the  more  concentrated  solution,  and  therefore  leaves 
a  denser,  more  closely  packed  mass.  In  the  weaker  solutions  the  mas.s 
originally  is  much  less  dense,  but  when  it  settles,  the  mass  may  appear  as 
dense  as  that  from  the  thicker  solution.  However,  in  the  weaker  solutions 
it  will  be  noted  that  the  supernatant  solution  is  often  cloudy,  turbid,  or 
opalescent  with  a  fine  precipitate  which  does  not  tend  to  settle  out.  In  the 
stronger  solutions,  this  may  be  carried  down  with  the  rest  of  the  flocculent 
precipitate,  or  else  in  the  stronger  solutions,  the  precipitated  granules  are 
larger.  A.  Fischer  ('99)  notes  that  the  thinner  the  solution  of  a  colloid,  the 
smaller  the  granules  precipitated  with  reagents. 

If,  then,  a  weaker,  but  not  necessarily  a  less  viscid  solution  of  a  colloid 
will  leave  less  precipitate  than  a  more  concentrated  one  when  thrown  down, 
then  the  strength  of  colloidal  solutions  in  tissues  can  be  judged  by  the 
amoutit  of  residue  they  leave  in  fixed  sections.  The  very  young  etiibryos 
show  a  much  more  semi-fluid  condition  when  picked  up  than  the  older  ones. 
Schafer  ('12,  p.  116)  points  out  that  the  albuminous  substances  of  the  cell 
interstices  of  very  young  embryos  later  acquire  a  muco-albuminous  char- 
acter, and  the  tissue  assumes  a  jelly-like  consistency.    Triepel  ('11)  describes 


RAXSOHUFF  MEMORIAL  VOLUME 


a  corresponding  series  for  fixed  sections,  a  fine  network   in   young  stages, 
which  becomes  coarser  as  the  embryo  grows  older. 

On  pressure  on  the  subcutaneous  connective  tissues  taken  from  a  four- 
to  seven-day  chick  mounted  between  a  cover-glass  and  slide  and  sealed  with 
\aselin.  pieces  can  be  made  to  separate  off  from  the  central  mass,  just  as 
])ieces  can  be  broken  ofif  of  a  "wobbly"  gelatin  gel.  If  the  microscope  it 
tilted,  these  pieces  will  slip  down,  accommodating  their  outline  to  the  sur- 
rounding obstacles.  Such  a  mass,  on  flowing  between  two  fixed  particles 
(as  pieces  of  glass),  will  be  drawn  into  a  very  narrow  thread  as  a  string 
of  ropy  mucus.  On  flowing  through,  it  is  reconstituted  or  regathered  as  a 
mass  as  soon  as  an  open  space  is  reached  (Fig.  4).  The  ease  with  which  a 
group  of  cells  separate  and  regather  with  little  or  no  trace  of  their  experi- 
ence, even  on  fixation,  suggests  that  the  syncytial  appearance  of  young  con- 
nective-tissue cells  is  a  temporary,  apparent  union  of  the  cells,  easily 
changed  by  the  conditions  of  the  environment.  It  is  not  impossible  to  im- 
agine  a   similar  process  taking  place   on   handling  and   fixing  an   embryo. 


Subcutaneous 
tissue 


Separation  of  cells 


Kig.  4.  Tissue  from  a  four-day  chick  allowed  to  slip  between  two  pieces  of  glass, 
while  inounted  under  a  cover-glass.  After  the  entire  mass  squeezed  through,  one  cell 
at  a  time,  fixation  shows  the  fibrils  intact  between  all  the  cells.  Camera-lucida  drawings. 


Lymphatic  vessels  and  capillaries  may  be  compressed,  cell  masses  pushed 
out  of  their  places,  adhesions  formed,  all  without  leaving  evidence  of  their 
original  condition.  This  may  be  one  way  of  interpreting  the  isolated  en- 
dothelial-lined  spaces  and  lymphatic  anlagen  described  by  Huntington  ('10). 
McCIure  ('10).  and  Kampmeier  ('12).  The  last  points  out  (p.  430)  thai 
"histologically  all  incipient  lynijihatic  anlagen  .  .  .  are  decidedly  dif- 
ferent from  either  an  active  vein  or  a  mature  lymphatic.  They  lack  definition 
and  possess  vague  and  undififerentiated  outlines ;  for  the  cells  of  their  walls 
are  not  arranged  in  that  end-to-end  fashion  so  characteristic  of  vascular 
endothelia.  Instead,  many  instances  were  observed  under  strong  magnifica- 
tion where  the  tissue  cells  in  their  longest  diameter  stand  perpendicular  to 

Page  -'-'} 


RAPHAEL  ISAACS 


the  periphery  of  the  anlagen  and  project  far  out  into  the  kimen  with  their 
cytoplasmic  filaments."  Kampmeier  interprets  this  condition  as  being 
brought  about  by  the  addition  or  fusion  of  contiguous  spaces.  However, 
these  regions  may  have  been  continuous,  and  the  apparent  interruptions  may 
have  resulted  from  adhesions  al  the  time  nf  fixation. 

The  adhesive  process  may  also  describe  the  segmentation  of  the  "retro- 
gressive venous  channels"  of  different  authors,  in  which  the  lumen  of  a 
vessel  is  interrupted  by  solid  cell  masses.  The  value  of  Kampmeier's  ob- 
servation (p.  433)  that  more  delicate  fibrils  lie  in  the  pathway  of  future 
lymphatics  is  evident,  as  it  is  proljable  that  these  represent  regions  of  less 
concentration  than  the  surrounding  tissue,  less  precipitate  having  been  left. 
Kainpmeier  (p.  451)  further  observes  that  "the  elongation  of  lymphatic 
spaces  and  their  fusion  finally  into  a  continuous  channel,  as  well  as  a  growth 
of  their  cavities  in  diameter  is  accomplished  by  the  .same  process  which  gave 
origin  to  them,  namely,  by  the  disintegration  of  tissue  fibrils  and  the  con- 
centric addition  of  .spaces."  The  coagulated  fibrils,  however,  as  sections 
show,  wall  off  spaces  in  one  dimension  only,  while  in  the  living  condition  the 
intercellular  colloid  is  continuous  throughout  the  region.  The  correspond- 
ence of  the  ages  of  the  individual  embryos  in  which  these  conditions  are 
found  indicates  that  the  intercellular  substance  in  certain  definite  plac.-s 
is  in  the  same  physiological  condition. 

Inasmuch  as  we  can  conclude  from  Kampmeier's  observations  that  less 
dense  regions  form  in  the  tissue  and  inasrnuch  as  we  have  considered  the 
mechanism  by  which  adhesions  can  be  brought  about,  we  have  a  physiologi- 
cal basis  for  the  distribution  of  growing  lymphatics  and  blood-vessels.  As 
the  free-flowing  blood  and  lymph  are  confined  to  vessels,  walled  in  by  en- 
dothelium, the  growing  ends  of  the  proliferating  capillaries  probably  follow 
the  lines  of  least  resistance  and  therefore  take  the  less  dense  pathway 
through  the  tis.sues.  It  is  conceivable  that  regions  where  oxidation  of  acid. 
or  their  neutralization  becomes  deficient,  the  tissue  would  absorb  more  water 
and  eventually  almost  liquefy,  allowing  a  growing  capillary  free  access,  and 
thus  automatically  establishing  a  better  circulation  for  that  part.  The  regions 
of  finer  fibrils  in  the  iiatlnvay  of  growing  capillaries  strongly  suggest  this 
view.  In  fixed  tissue  it  is  not  possible  to  make  observations  on  the  small 
changes  in  hydrogen  ion  concentrtion  necessary  to  influence  the  tissues. 
These  changes  may  be  exceedingly  small,  as  shown  by  their  influence  on  the 
secreting  mechanism  of  excised  kidneys  (Isaacs,  '17).  Furthermore, 
"young"  capillaries  of  the  blood  and  lymph  system  do  not  show  concentric 
layers  of  connective  tissue  around  them  as  do  the  larger  vessels  which  have 
increased  their  size  in  situ,  or  more  solid  organs  as  the  thyroid,  thymus,  ■ir 
the  salivary  glands  in  the  embryo,  showing  that  little  or  no  compression  took 
place  as  the  capillary  grew  in  (Figs.  1  and  5).  This  holds  true,  even  though 
we  take  into  account  the  contraction  on  fixation. 


RAXSOIIOI-'I-  MEMORIAL  VOLUME 


THE  FIBER  PRODUCING  CELLS. 
Of  cellular  constituents,  the  spindle  shape  is  apparently  the  more  stable 
form.  The  multipolar  forms  can  be  considered  as  response  forms  caused  hv 
the  conditions  of  the  environment  at  any  given  moment.  Ferguson  ("12) 
and  Clark  ('12)  have  described  the  changes  of  shape  of  living  connective- 
tissue  cells,  and  their  work  points  to  the  independent  movement  of  these 
cells.  Ferguson  (p.  134)  notes  a  change  from  round  to  stellate  and  stellate 
to  round.  In  chick  tissue,  however,  most  of  the  cells  take  a  short  spindle 
form  when  surrounding  tension  and  pressure  is  released.  Ferguson's  (p. 
135)  observation,  that  "the  shape  of  tlie  cell  (stellate  type)  is  undoubtedh 
influenced  to  some  extent  by  its  surroundings,  and  the  duration  of  a  par- 
ticular stellate,  spindle  or  lamellar  shape  may  in  some  cases  be  thus  de- 
termined," can  be  demonstrated  by  \arying  the  pressure  on  the  cover-glass 
in  a  tissue  mount.     His  statement  that  "the  general  trend   from  round  t.) 


Fibr  n  ..  (         /^J\    Connect  ve 


""T"'  .fcf  t ' 


-  y-i.       i  S/ 


^ 

Fig.  5.  Connective-tissue  tibrils  and  fibrin  in  subcutaneous  tissue  of  55-inm.  pig 
embryo.  Fixed  in  Bouin.  Stained  in  Mallory's  connective-tissue  stain  and  iron 
haematoxylin.     Camera-lucida  drawing. 

Stellate  and  from  stellate  to  spindle  is  inevitable"  is  significant  in  indicating 
the  changes  of  tension  in  the  growing  embryo.  Rous  and  Jones  f'16)  de- 
scribe a  series  of  changes  taking  place  in  cells  freed  from  connective  tissue 
by  digestion  with  3  per  cent  trypsin  solution.  Under  these  conditions,  the 
cells  tend  to  become  spherical.  In  our  preparation  we  can  also  make  the 
cells  assume  a  more  spherical  form  if  any  solution  is  added  which  contains 
more  free  water  than  the  normal  environment  of  the  cells.  This  does  take 
place  of  itself  as  soon  as  the  water  of  syneresis  forms  in  our  preparations, 
as  described  before. 

From  the  fact  that  in  fresh  mounts  most  of  the  multipolar  or  stellate 
cells  on  release  from  the  tissue,  before  any  stiffening  takes  place,  assume 

Page  -'-'« 


RAPHAEL  ISAACS 


the  spindle  forms,  we  can  assume  that  the  factors  affecting  the  shape  of  these 
cells  are  the  pulls  and  pushes  affecting  the  region.  Change  in  shape  of  a 
cell  thus  accompanies  a  change  in  surroundings.  A  comparison  of  the  more 
compact  mesenchymal  tissue  (greater  number  of  nuclei  per  unit  area)  of  a 
10-mm.  stage  with  that  of  a  30-mm.  pig  shows  the  latter  to  be  looser,  in 
spite  of  the  fact  that  the  growing  internal  organs  take  up  increased  space 
and  taking  into  consideration  the  contraction  of  the  outer  layers  on  fixin;;. 
Evidently  the  tension  changes  as  the  embryo  grows.  Clark  ('12.  p.  366)  docs 
not  conclude  that  the  change  in  position  of  individual  cells  can  be  accounted 
for  only  on  a  basis  of  general  growth.  When  a  piece  of  tissue  is  pushed 
with  a  needle  under  the  misroscope,  the  mucoid  nature  of  the  mass  causes 
it  to  react  as  a  whole,  each  cell  being  affected  by  the  surrounding  push  just 
as  much  as  the  surrounding  colloid.  However,  the  cells  are  in  a  temporary 
stage  of  unstable  equilibrium,  and  gradually  work  their  way  in  the  colloid 
until  they  have  reached  the  most  stable  position  for  the  new  set  of  conditions. 
.\  demonstration  of  this  process  is  seen  in  the  descent  of  a  piece  of  lead 
through  a  gelatin  gel,  or  the  conditions  may  be  better  illustrated  with  a  watch 
spring  enibedd-ed  in  gelatin  of  such  a  .strength  that  the  two  bend  together. 
After  bending,  the  spring  will  eventually  straighten  itself  by  workin;,' 
through  the  gelatin.  This  process,  which  is  really  diapedesis,  is  probably 
the  mechanism  by  which  tissues  are  shaped  in  response  to  pressure  or  tension 
stimuli. 

As  the  tissue  grows  older,  it  becomes  denser,  the  jelly  becoming  thicker, 
and  response  to  pulls  and  pushes  by  permanent  change  in  form  less  marked, 
because  the  cells  have  less  freedom  in  the  thicker  jelly.  Kaneko  ('04)  de 
scribes  this  in  granulation  tissue,  is  which  the  direction  of  the  fibers  which 
may  be  formed  is  influenced  by  the  direction  of  stresses  or  pulls,  while  this 
response  is  lost  in  fully  formed  connective  tissue. 

It  is  of  course  a  matter  of  general  experience  that  embryos  shrink  in 
fixing  or  during  the  dehydration  process.  While  this  accounts  for  some  of 
the  compression  of  layers  immediately  underlying  the  skin  and  around  the 
more  solid  organs,  some  is  no  doubt  due  to  the  fact  that  organs,  as  the 
glands,  in  their  growth,  glide  into  the  connective-tissue  jelly,  which  is  first 
compressed  and  then  readjusted  to  the  new  conditions.  Sections  often  show 
the  connective  tissue  compressed,  yet  separated  by  spaces  from  such  organs 
as  the  salivary  glands  or  thyroid,  the  space  being  bridged  here  and  there  by 
fibrils.  This  can  be  interpreted  as  indicating  that  there  is  no  firmer  union 
between  the  connective  tissue  and  the  gland  other  than  that  of  the  gener;il 
stickiness,  due  to  the  viscous  intercellular  substance.  The  relation  of  d 
gland  to  the  surrounding  connective  tissue  may  be  illustrated  with  gelatin 
solutions.  A  strip  of  a  4  per  cent  gelatin  gel  is  immersed  in  a  2  per  cent 
gelatin  sol.  and  the  latter  allowed  to  gel,  or  it  may  be  treated  with  a  fixative. 
It  will  be  found  that  tlie  fir.st  strip,  which  is  optically  well  marked  off  from 
its  surroundings,  retains  its  identity,  and  on  being  pulled  out,  retains  some 

Page  -vr 


RAXSOHOFF  MEMORIAL  VOLUME 


of  the  weaker  gelatin  sticking  to  it.  However,  this  can  be  wiped  off  and  the 
two  separated.  This  expresses  the  relation  of  a  growing  gland  to  the  con- 
nective tissue. 

The  ease  with  which  embryonic  connective-tissue  cells  (four-day  chick) 
can  be  separated  in  the  fresh  condition  indicates  that  their  syncytial  appear- 
ance is  due  to  adhesion.  Ferguson  ('12)  has  observed  the  union  of  cell 
processes  in  living  fundulus  embryos,  and  Clark  ('12)  has  mapped  out  their 
successive  space  relations  in  growing  tadpoles.  Under  such  circumstances, 
fibrils,  if  present,  would  either  anchor  the  cells  or  else  leave  a  visible  trail 
of  the  ceil  passage.  However,  in  sections  they  surround  the  cells  on  all 
sides,  with  no  appearance  as  the  tail  of  a  cement,  that  we  would  expect 
under  the  circumstances.  On  killing  the  tissue,  contraction  and  great  shrink- 
age often  results  in  the  separation  of  the  connective-tissue  cells,  so  that  many 
investigators,  not  being  able  to  trace  the  connection  from  one  cell  to  another, 
have  concluded  that  the  cells  fade  out  into  the  fibrils. 

THK   "KIBRll.S"   .\X1)    FIBER    FOKMATIOX. 

That  the  fibrils  are  artificial  coagulation  products  may  be  inferred  from 
the  dit^'erence  in  delicacy  of  the  pattern  with  different  fixatives  (Fig.  2,  B, 
D,  E,  F).  Triei^cl  ("11)  notes  this  variation  with  the  fixatives  in  studying 
connective-tissue  fibrils  and  that  of  the  coagulum  in  the  blood-vessels  in  a 
given  region  in  an  embryo  is  somewhat  the  same.  Triepel  ('11)  calls  at- 
tention to  the  remarkable  constancy  of  the  pattern  and  its  characteristic 
formation.  This  is  of  course  natural,  if  the  fibrillae  are  products  precipi- 
tated by  the  fixatives.  However,  he  attributes  the  different  sizes  of  the 
fibrillar  details  to  different  amounts  of  shrinkage  caused  by  different  fixa- 
tives in  preexistent  fibrils.  Hansen  ("99)  recognizes  "pseudofibrillae"  of 
cartilage  as  artifacts  ("alcohol  fibers"  of  Solger),  but  does  not  apply  the 
principle  to  connective-tissue  fibrils. 

The  fibrils  take  a  golden-yellow  color  with  orange-G,  a  light  jiink  with 
acid  fuchsin,  and  a  blue  with  the  aniline  blue  in  Mallory's  connective-tissue 
stain.  With  the  latter,  the  bodies  of  the  connective-tissue  cells  stain  pink  or 
orange-pink.  (Fergu.son  ('11)  describes  the  collagenous  fibrils  as  taking  a 
golden-brown  color  with  Bielschowsky's  silver  method.  From  the  foregoing 
description  of  the  origin  of  the  fibrils  as  precipitation  products,  we  car. 
account  for  the  variation  in  results  with  silver-impregnation  methods.  The 
fibrils  cannot  be  demonstrated  in  the  fresh  mount  with  any  of  the  above 
stains  nor  with  the  so-called  vital  stains,  until  subsequent  changes,  possibly 
dehydration,  lead  to  fibril  formation. 

The  more  solid  elements  of  the  tissue,  including  the  white  fibrous,  the 
yellow  elastic  and  the  precartilage  tissue,  are  formed  from  the  intercellular 
jelly  by  the  depostion  of  more  material,  making  the  jelly  more  concentrated, 
thus  leaving  more  precipitate  in  fixed  sections.  The  gelation  and  stiffening 
of  the  white  and  elastic  fibers  can  be  easily  followed  in  the  fresh  subcu- 


RAPHAEL  ISAACS 


taneous  tissue  and  tendons  of  the  chick.  Fresh  preparations  are  mounted 
between  the  slide  and  cover,  sealed,  and  examined  immediately.  Twelve- 
day  chicks  and  those  just  hatched,  illustrate  the  stages.  While  one  watches 
through  the  microscope,  slight  pressure  on  the  cover  will  serve  to  separate 
pieces  of  tissue.  Elongated  strands  of  tissue,  stretching  from  piece  to  piece, 
may  be  seen,  with  occasional  spindle-shaped  swellings.  Analysis  shows  that 
these  swellings  represent  connective-tissue  cells,  adhering  to  a  stifif,  jelly- 
like strand  of  the  intercellular  substances.  On  further  separation,  the  strand 
apparently  elongates.  The  fiber  is  very  sticky  at  this  stage.  The  older  stages 
show  that  the  connective-tissue  cells  are  adhering  closely  to  a  well-formed 
fiber,  and  can  be  dragged  along  the  fibers  when  tension  is  put  upon  them. 
The  fiber  is  formed  of  the  jelly  between  the  cells,  and  the  increase  in  tough- 
ness from  a  viscid  state  to  a  well-formed  fiber  is  shown  by  its  changes  of  ex- 
tensibility and   consistency   in  the   fresh  and  the   varying  intensity   of   the 

Fibers  in  fresii  tissue 


Fig.  6.  Appearance  of  libers  in  a  si.\teen-day  chick,  when  flattened  under  a  covei' 
glass.  Successive  ages  are  shown  (A)  before  and  (B)  after  fixing.  Camera-lucid; 
drawings. 


staining  reactions  in  the  fixed  tissue.  In  the  early  stages,  a  well-formed 
young  fiber  can  assume  the  appearance  of  a  thick  network,  if  it  is  treated 
with  a  coagulating  or  dehydrating  fluid  (Fig.  6).  In  the  latter  stages  the 
jelly  becomes  thick  enough,  so  that  the  holes  remain  when  cells  or  muscle 
fibers  are  pulled  out  in  manipulating  the  tissue.  The  sections  indicate  a 
progressive  increase  in  concentration  due  to  deposition  of  more  material,  i 
fact  shown  by  the  increase  in  the  amount  of  intercellular  precipitate  in  sec- 
tions. The  fibers  are  first  laid  down  close  together  in  sheets  or  ribbons  and 
separate  into  the  familiar  strands  only  after  the  expansion  of  the  surround- 
ing areas.    Fixation,  of  course,  separates  them  by  shrinkage. 


RA.VSOHOFF  MEMORIAL  VOLUME 


The  speed  of  decolorization  after  staining  is  a  factor  in  considering  rela- 
tive densities.  The  small  fibrils  lose  their  stain  sooner  than  the  larger,  and 
the  white  fibers  last  of  all.  A.  Fisher  ('99)  and  Mann  ('02).  however, 
suggest  that  the  greater  relative  surface  of  small  particles  over  larger  ones, 
in  comparison  to  their  volume,  allows  greater  space  for  washing  out  of  the 
stain.  No  fibrils  can  be  demonstrated  in  the  early  or  later  stages,  nor  doei 
jaiiis  green,  methylene  blue,  or  neutral  red  show  their  presence.  The  edema 
set  up  by  the  use  of  aqueous  solutions  of  these  salts  may  be  temporarily 
avoided  by  dusting  a  few  grains  of  the  powdered  stain  on  the  tissue.  Tlie 
diffusion  of  the  stain  brings  about  the  result  desired  from  the  aqueous  so- 
lution by  emphasizing  the  difference  of  refraction  of  the  different  constitu- 
ents. As  different  authors  have  pointed  out,  the  vital  stains  of  this  type  act 
only  on  tissue  which  has  already  begun  to  die.  Granules  may  dissolve  som. 
of  the  stain  without  killing  the  cell,  however.  Paramoecium,  in  which  the 
posterior  end  is  dead  and  consequently  stained  deep  pink  with  neutral  red. 
still  retain  their  power  of  movement.  Fundulus  eggs  can  be  grown  in  toxic 
solutions  of  substances,  often,  however,  with  the  production  of  abnormalities. 
The  continuation  of  one  or  more  of  the  vital  processes  of  a  cell  cannot  be 
considered  as  a  test  of  the  normality,  so  that  results  with  vital  stains  belong 
to  the  observations  on  experimental  tissue,  not  necessarily  normal. 

The  cells  are  probably  the  active  agents  in  influencing  the  deposition  of 
the  material.  The  modern  simile  of  an  assembling  and  distributing  plant 
probably  describes  the  function  of  the  cells  in  handling  the  materials  in  fiber 
formation.  The  movement  and  migration  of  the  cells  probably  afifect  the 
distribution  of  the  fibers  and  result  in  forming  strands  of  the  fibers,  instead 
of  one  mass.  The  subsequent  pulls  and  movements  of  the  part  as  a  whole 
cause  the  strands  to  glide  over  one  another,  and  this  is  probably  a  second 
factor  in  the  isolation  of  fibers.  The  appearance  of  fibers  can  thus  be  simu- 
lated in  a  gelatin  or  fibrin  gel.  There  is  some  evidence  to  lead  one  to  think 
that  the  cells  are  definitely  polarized  with  respect  to  fiber-producing  regioi'S, 
thus  accounting  for  the  fact  that  some  regions  remain  more  jelly-like  while 
neighboring  regions  around  the  same  cell  stiffen.  The  cell  in  profile  is  flat- 
tened on  the  fiber  side,  but  convex  on  the  jelly  side. 

Optical  effects  may  be  obtained  with  different  concentrations  of  gelatin, 
giving  the  same  contrast  relations  that  are  found  in  fresh  tissues.  If  cubes 
of  water-soaked  gelatin  of  the  same  size  are  treated  with  dehydrating  or 
hydrating  agents  of  different  strength  (grades  of  alcohol,  commercial  forma- 
lin, \'an  Gehuchten's  alcohol-acetic-chloroform,  or  corrosive  sublimate), 
blocks  of  varying  density  are  obtained.  The  greater  the  density,  in  this  case, 
the  greater  the  refractiveness  (Isaacs,  '16).  In  other  words,  the  greater  the 
density  of  a  colloid  of  this  type  in  the  tissue,  the  greater  its  refractiveness 
and  the  lighter  it  appears  when  in  focus  under  the  misroscope.  It  is  for 
this  reason  that  the  cell  nuclei  and  fibrils  as  well  as  other  elements  appear 
clearer  when  the  preparation  is  allowed  to  stand  and  undergo  coagulation 
and  dehydration  changes.    The  change  is  a  real  one,  and  is  not  merely  due. 

Page  230 


RAPHAEL  ISAACS 


as  has  often  been  suggested,  to  the  eye  becoming  accustomed  to  the  prepara- 
tion. 

The  suggestion  naturally  follows  that  the  fibrils  may  have  been  present 
as  slightly  more  concentrated  areas  in  the  interstitial  connective  substance 
and  escape  detection  while  observed  in  the  fresh  tissue.  Maxinow  ('06)  de- 
scribes the  ground  substance  as  homogeneous,  with  granules  which  prob- 
ably represent  a  network.  Danchakofif  ('08 j  considers  that  the  spaces  left 
in  sections  are  due  to  extration  or  dissolving  out  of  the  intercellular  sub- 
stance. While  considering  the  action  of  reagents  as  accounting  for  some 
granular  deposits,  Danchakofif  describes  the  fibrils  as  cell  processes.  How- 
ever, the  precipitating  action  of  reagents  can  be  seen  under  the  microscope 
by  applying  them  with  a  delicate  pipette  to  the  undersurface  of  a  hanging- 
drop  preparation,  thus  avoiding  the  danger  of  "washing  out."  The  action 
is  seen  to  be  one  of  condensation  and  precipitation  of  the  dissolved  material, 
leaving  the  fluid  part  in  the  meshes  of  the  resulting  granular  coagulum.  The 
results  can  be  checked  up  with  stains. 

Hober  ('14)  states  that  structures  produced  in  gelatin  by  alcohol  are  not 
preformed,  but  are  produced  on  dehydration.  In  order  to  see  if  the  fibrillae 
were  performed  or  were  artifacts,  the  tissue  (skin,  subcutaneous  tissue. 
or  muscle  of  a  chick  embryo)  was  pressed  free  from  blood  and  lymph,  and 
then  irrigated  with  a  potassium  oxalate  salt  solution  (Ringer's  solution  with 
potassium  oxalate  substituted  for  the  calcium  chloride,  an  empirical  solution) 
and  the  solution  filtered.  A  similar  solution  can  be  made  by  allowing  con- 
nective tissue  to  stand  overnight  in  a  little  Ringer's  solution.  Treating  u 
drop  of  this  solution,  after  filtering,  with  absolute  alcohol  or  Zenker's  so- 
lution on  a  slide,  a  complete  network,  resembling  that  of  the  tissue  fibriU, 
was  obtained,  and  it  took  the  fibrillar  stains  (Fig.  2.  A).  Extracts  from  most 
tissues  can  be  precipitated  in  the  same  way,  giving  fibrillar  structures  char- 
acteristic of  each  tissue.  The  fact  that  a  complete  network  was  obtained  in 
this  case  would  seem  to  indicate  that  the  fibrillar  network  was  an  artificial 
precipitation  product.  Fixation  of  the  washed  tissue  shows  a  decrease  in 
the  number  of  fibrils.  The  substance  which  was  filtered  evidently  contained 
material  from  the  more  fluid  intercellular  substance.  It  is  to  be  expected 
that  this  contained  the  same  serum  albumin,  serum  globulin,  and  fibrinogen 
that  we  normally  find  in  the  blood  and  lymph,  and  this  in  the  end  is  probably 
the  key  to  the  network  formation  between  the  connective-tissue  cells.  The 
presence  of  some  mucin-like  substance  alters  the  staining  reaction  somewhat 
and  enables  us  to  differentiate  it  from  pure  lymph  coagulum.  A  similar 
substance  and  a  similar  network  may  be  encountered  in  any  tissue.  The  net- 
work bears  the  same  relation  to  the  intercellular  jelly  as  the  crystal  colonv 
bears  to  the  solution  from  which  it  develops  and  is  specific  for  each  of  the 
different  colloids  under  the  same  conditions. 

Fleming  ('97)  and  others  maintained  that  the  fibers  were  transformations 
of  the  eel  protoplasm,  Meves  ('10)  specifying  their  orgin  from  chondrioconta 
at  the  cell  surface. 


RANSOHOFF  MEMORIAL  VOLUME 


FRAMEWORK  OF  ORGAN'S. 

The  digestion  method  of  demonstrating  fibrils,  as  applied  by  !\Iall  ('92') 
and  others,  takes  advantage  of  the  fact  that  the  fibrils  apparently  resist 
pancreatic  digestion  in  alkaline  solution.  Mall  ('02)  finds  that  unfixed, 
frozen  sections  which  are  digested  are  difficult  to  stain  in  any  satisfactory 
way,  due  to  mechanical  difficulties.  He  obtained  a  better  picture  in  alcohol - 
fixed  tissue.  Flint  ('04)  suggests  the  use  of  alcohol-chloroform-acetic  acid, 
sublimate  acetic,  or  alcohol  alone  to  show  the  "fibrillar  framework"  of  organs 
by  pancreatic  digestion.  Formalin  cannot  be  used  for  this  purpose.  It  will 
be  noticed  that  those  reagents  best  suited  for  this  demonstration  coagulate 
the  homogeneous  connective-tissue  colloids  under  the  microscope  into  the 
hard  definite  connective-tissue  fibrils.  Zenker's  solution,  while  showing  the 
fibrils,  presents  secondary  difficulties  which  bar  its  use  in  digestion  work. 
Sublimate  solutions  and  chromium  salts  cannot  be  used  advantageously  in 
studying  connective  tissue,  as  the  coagu.ated  colloids  fringe  the  cells  with 
fibrils,  thereby  covering  up  many  details. 

Fresh  tissues  exposed  to  several  changes  of  an  alkaline  solution  of  pan- 
creatin  for  varying  lengths  of  time  (from  days  to  weeks)  without  any 
preservative,  but  conducted  under  aseptic  conditions,  do  not  show  the  fibrillae 
when  mounted  under  the  microscope.  Instead,  we  have  a  uniform  jelly 
between  the  white  fibers  and  the  spaces  occupied  by  the  cells.  The  fibrillae, 
however,  can  be  made  to  appear  by  dehydrating  or  coagulating  agents.  Thi; 
enables  us  to  interpret  Mall's  ('02)  results  when  he  finds  that  the  digestion 
method  "causes  the  sections,  if  fresh,  to  become  a  swollen  and  slimy  mass 
in  which  the  delicate  fibrils  can  be  seen  after  it  is  treated  with  picric  acid." 
Picric  acid  precipitates  the  fibrils  from  solution.  A  consideration  of  the 
following  test-tube  experiments  may  be  helpful  in  this  connection.  If  fresh 
albumin  is  digested  in  an  alkaline  solution  of  pancreatin,  a  clear  solution  re- 
sults. The  addition  of  alcohol  or  sublimate  acetic  results  in  a  flocculent 
precipitate  (peptones).  Therefore,  if  any  product  of  digestion  remain  in 
the  homogeneous  jelly  resulting  from  digestion,  we  can  have  just  as  com- 
plete a  network  formed  as  if  no  digestion  took  place.  Posner  and  Gie.s 
('04)  point  out  that  the  "connective-tissue  mucoids  are  readily  digested  by 
trypsin  in  alkaline  solution."  If  the  washing  is  complete  enough  to  remove 
the  products  of  digestion,  then  the  tissue  falls  to  pieces  and  the  results  are 
considered  "unsatisfactory."  The  unreliability  of  digestion  methods  is  a 
part  of  the  experience  of  all  who  have  used  them.  This  would  indicate 
the  possibility  that  the  fibrillar  details  in  the  framework  of  organs  and  base- 
ment membranes  may  be  products  of  fixation.  Mall  ('92),  Flint  ('04),  and 
Moody  ('10),  among  others,  give  excellent  descriptions  of  such  digestion 
preparations,  which,  if  considered  from  the  point  of  view  of  coagulation 
products,  indicate  something  of  the  distribution  of  the  iiUercellular  colloid. 

Page  2SZ 


RAPHAEL  ISAACS 


NEUROGLIA    AND    THE    INTERCELLULAR    TELLY    OF    THE    NERVOUS 
SYSTEM. 

The  jelly-like  nature  of  fresh  nervous  tissue,  as  the  cerebral  hemispheres 
of  the  adult  frog  or  its  medulla,  is  a  constant  characteristjc.  This  tissue 
when  mounted  fresh  between  a  slide  and  cover  and  sealed  shows  a  field 
of  cells,  nuclei,  and  nerve  fibers  imbedded  in  a  clear  homogeneous  jelly.  By 
varying  the  pressure,  difTerent  details  can  be  brought  out.  If  some  alcohol 
is  allowed  to  run  under  the  cover,  the  picture  changes  entirely.  A  heavy 
groundwork  of  very  delicate  fibrils  develop  both  in  the  tissue  and  in  the 
expressed  jelly  surrounding  it.  The  nerve  fibers  often  act  as  bases  around 
which  and  from  which  the  fibrils  radiate.  Van  Gehucten's  fluid  gives  an 
equally  heavy  crop  of  fibrils.  The  presence  of  different  structures,  as  capil- 
laries, active  ciliated  cells,  and  nerve  fibers,  serve  often  to  give  a  clue  as  to 
just  what  part  of  the  brain  wall  we  are  studying. 

Hardesty  ('04)  points  out  that  the  development  of  the  neuroglia  fibers 
is  a  process  of  transformation  of  fibrillated  areas.  The  deeply  stained 
fibers  in  the  exoplasm  of  the  syncytium  of  his  sections  are  seemingly  derived 
from  a  condensation  of  the  less  deeply  staining  substance.  However,  a 
study  of  the  fresh  tissue  leads  to  the  conclusion  that  this  described  for- 
mation is  really  the  result  of  precipitating  the  successive  stages  with  thf. 
fixative.  The  increase  in  concentration  and  density  brought  about  by  ad- 
dition and  deposition  of  more  material  to  the  jelly  gives  us  a  basis  for  varia- 
tions in  the  pictures  obtained  in  successive  stages.  Coagulation  or  fixation, 
then,  would  leave  a  more  compact  mass  where  the  fibers  are,  but  a  delicate 
network  ("fine  threads  of  the  spongioplasmic  network"  (p.  262)  in  the 
less  concentrated  parts.  This  work  corroborated  Weigert's  and  Hardesty's 
(p.  257)  conclusion  that  "the  fibers  cannot  be  regarded  in  any  sense  as  out- 
growths of  the  cells,"  but,  on  the  other  hand,  it  indicates  that  we  are  dealing 
with  more  or  less  concentrated  colloids  of  the  homogeneous  intercellular 
substance  and  that  the  fibrillated  appearance  of  the  so-called  exoplasm  is  a 
fixation  product.  Holmgren  ('04)  and  later  Ross  ('15)  have  described 
prolongations  of  cytoplasmic  processes  of  glia  cells,  which  appear  in  section 
to  run  into  the  "trophospongia"  of  the  nerve  cells.  These  apparent  "non- 
nervous  partitions  of  capsular  processes  continuous  with  the  glia  cell"  are 
in  reality  the  remains  of  the  intercellular  jelly  which  when  coagulated  by  the 
fixative  or  in  post-mortem  processes  appear  to  be  fine  protoplasmic  fibrillae 
continuous  with  the  glia  cells  on  the  one  hand  and  the  tro]ihospongia  on  the 
other. 

SU.\nLARY  AND  CONCLUSIONS 

The  intercellular  jelly  of  embryonic  and  adult  tissue  is  structurallv 
homogeneous  and  contains  no  network  of  fibrils.  The  evidence  may  b.- 
summoned  up  as  follows : 

1.  Fibrils  cannot  be  seen  in  the  living  intercellular  substance. 

2.  Fixatives,  drying,  dehydration,  or  coagulating  reagents  are  necessary 
to  show  the  fibrillae. 

Page  2.M 


RANSOHOFF  MEMORIAL  VOLUME 


3.  In  young  embryos  llie  cells  may  he  rearranged  by  manipulation  of  the 
tissue,  but  on  fixation  the  fibrils  are  continuous. 

4.  The  process  of  fibril  formation  can  be  followed  under  the  micro 
scope. 

5.  The  possibility  of  ■"wasliing  out"'  a  non-coagulated  colloid  from  tiie 
meshes  of  a  network  can  be  eliminated  by  fixing  the  tissues  under  the 
microscope. 

6.  The  form  and  structure  of  the  network  varies  with  the  fixative. 

7.  Cut  pieces  of  tissue  ])laced  in  contact  and  fixed  show  a  cuntinuity 
of  fibrils. 

8.  Intercellular  jelly  wasiied  out  and  passed  through  a  filter  can  be 
precipitated  as  a  complete  network  with  the  ordinary  fixatives. 

9.  Complete  washing  out  of  the  intercellular  jelly  gives  a  fibrillar- 
free  picture  when  the  tissue  is  treated  with  fixatives,  while  the  filtrate  can  be 
made  to  precipitate  as  a  fibrillar  network. 

10.  Digestion  methods  do  not  show  the  fibrils  unless  some  step  in  the 
technique  involves  a  coagulating  or  dehydrating  process. 

11.  Complete  and  similar  fibrillar  networks  can  be  obtained  h\  the  ac- 
tion of  fixatives  on  pure  solutions  of  gelatin,  mucin,  plasma,  egg-albumni 
and  other  solutions. 

12.  While  the  density  of  the  network  increases  with  the  age  of  the 
tissue,  the  process  is  reversed  when  ])ost-mortem  digestion  or  acidosis  is 
allowed  to  proceed.  The  state  of  the  colloid  at  the  time  of  fixation  deter- 
mines the  type  of  fibrils. 

13.  Cells  may  move  freely  in  certain  embryonic  stages,  and  sections 
show  no  track  left  by  the  passing  cell  in  among  the  fibrils. 

14.  In  fixed  and  sectioned  tissue  the  cells  and  their  processes  and  fibers 
show  by  their  alignment  the  evidence  of  pressure  or  pulls.  The  "fibrils." 
however,  radiate  in  all  directions  unclianged  and  do  not  show  stress  lines. 

The  consideration  of  connective  tissue  and  neuroglia  fibrillae  as  fixation 
artifacts  is  of  aid  in  accounting  for  the  following  phenomena: 

1.  Movement  of  cells.  Diajjedesis.  (The  jiathway  is  a  structureless- 
jelly.) 

2.  Progressive  increase  in  strength  with  age.  from  the  jelly-likij 
younger  embryos  to  the  tougher  adult  tissues. 

3.  Non-ai)pearance  of  fibrillae  in  the  living,  with  their  ai»])earance  in 
fixed  tissue. 

4.  The  variation  in  the  fibril  pattern  when  dift'erent  fixatives  are  used. 

5.  The  similarity  of  pattern  of  fibrin  in  the  blood-\essels  and  fibrillae 
between  the  cells. 

6.  The  similarity  of  many  of  the  staining  reactions  of  the  fibrillae  and 
fibrin.    Those  stains  which  stain  the  mucoid  element  serve  to  differentiate. 

7.  Accommodation  of  the  connective  tissue  to  the  iiuading  cells  of 
growing  organs. 

Payf  m 


RAPHAEL  ISAACS 


8.  The  appearance  of  isolated,  fluid-filled  spaces  lined  by  endothelium  in 
the  connective  tissue. 

9.  \'ariation  in  the  behavior  of  successive  sections  or  "siiiiilarlv"  treated 
pieces  of  tissue  when  subjected  to  pancreatic  digestion. 

10.  "Superiority"  of  fi.xed  tissue  over  fresh  tissue  for  demonstrating 
"fibrillar  structures  of  frameworks  of  organs'"  Ijy  means  of  digestion 
methods. 

11.  The  variation  of  behavior  of  fibrils  to  Rielschowsky's  silver  method. 

12.  The  appearance  of  fixed  tissue  of  cells,  much  smaller  than  when 
alive,  apparently  fading  out  into  fibrillae. 

13.  The  clear-cut  lines  of  separation  when  connective  tissue  shrinks 
away  from  the  more  solid  cell  masses  on  fixation,  lea\'ing  a  few  fibrillae 
bridging  the  gap. 

14.  The  stickiness  of  living  connective-tissue  substance  and  connective- 
tissue  cells. 

15.  The  increase  in  density  of  the  fibril  network  with  age.  The  more 
concentrated  a  colloid,  the  thicker  the  network  that  is  formefl  on  ]jrecipita- 
tion. 

16.  The  varying  observations  on  basement  membranes. 

17.  The  appearance  of  ribbon-like  fibers  in  the  fresh,  which  turn  into 
a  thick  network  of  fibrils  on  fixation. 

18.  The  appearance  of  neurogliar  fibrillae  ("cell  i)rocesses"j  extending 
into  trophospongia  of  nerve  cells.  The  pecipitation  of  the  intercellular 
colloid  is  a  simpler  explanation. 

The  fibers  of  adult  tissues  are  formed  by  the  thickening  (concentration 
increase)  of  the  colloid  lying  between  the  fibroblasts.  The  polarization  ot 
the  cells,  their  movement  and  the  stress  exerted  on  the  growing  tissue,  all 
serve  to  give  the  adult  white  fibers  their  arrangement  as  strands  in  a  bundle. 
This  method  of  fiber  formation  enables  us  to  understand  the  shrinkage 
which  accompanies  fibrosis  in  the  tissues.  If  we  accept  the  fact  that  a  less 
dense  colloid  leaves  lighter  fibrils  than  a  more  concentrated  one,  then  we 
have  a  means  of  telling  the  consistency  of  tissues  when  the  fixed  sections 
are  studied.  A  physiological  determinant  is  also  supplied,  directing  the  d's- 
tribution  of  new  capillaries  along  the  lines  of  least  resistance. 


MTERATURE  CITED. 

Caitse'l,    1915.      The   origin   ai 

id   str 

uctur( 

;   of   a   fibrous 

tissue    which    appears   in    liv 

in 
g 

dturi 
1 

of  adult  frog  tissues.     Jour.   Exp. 

Med., 

vol. 

21,   p.   479. 

Bell,  1909.     On  the  histogene 

sis  of 

adipc 

>se  tissue  of  t 

he  ox.      Am.  Jour.   Anat.,   vo' 

1.9,   p 

1.    421 

Biitschli,    1892.     Mikroscopische    Sh; 

Leipzig. 

Clark,    E.    R.,    1912.     Further 

obser 

vation 

s    on    living    g 

rowing    lymphatics:    their    reU 

ition    1 

to   th 

^enchyme   cells.      Am.    Tour.    An; 

«..  vol.    1.?. 

p.    3(.0. 

l>.inchakoff,   1908.     TIntersuch. 

jnBcn 

ilber 

die   Fntwicklu 

iiK  von  Blut  und  Bindgewebe 

bei  V 

ogeli 

A,-c 

:h.    f.   mikroscopische   Anatomie   ' 

Li.  Ent 

vvickl 

Lingsmechanik, 

Bd.  73,   S.  147. 

Ferguson,   1911.     The  applicat 

ion   of 

the  : 

5ilver-inn)regna 

ition  method  of  Bielschowsky 

to  ret 

iicula 

Anat 

..  vol.  1.'.  p.  : 

!77. 

Ferguson,    1912.     The  behavio 

r   and 

relat 

ion   of   living  . 

connective-tissue  cells   in   the 

fins   c 

,f    fis 

embryos,    with   special    reference   to 

.   the 

h.stog 

enesis   of   the 

collaginous   or    white    fibers. 

Am. 

Joui 

An: 

it,    vol.    13,    p.    129. 

Fischer,    A.,    1899.     Fixirung, 

Farb 

ung    und    Bau    des 

Protoplasnia.    Jena,    S.    lA-2(i 

Fischer,    M.    H.,    1915.      Oede. 

na   an. 

rl   Nephritis,   2nd   e( 

1.,    New    York,    p.    240. 

RANSOM  OFF  MEMORIAL  VOLUME 


Fleniming,    1897.     Quoted    from    Schafer:    Text-book    of    Microscopic    A 

naloiny.     11th    ed..    N,;' 

York.    1912. 

Flint.    1904.      The    connective    tissue    of    tlie    salivary    glands    and   pancre 

as    with    its   devehipnien 

in    the   glandula   submaxillaris.   Johns    Hopkins   Hospital    Reports,   vol.    12,    p. 

8. 

Hansen.    1899.     L'ber   die    Genese    einiger    Bindgewebsgrundsubstanzen. 

.\natomische    .\nzeigcr 

•12-). 

Hardesty.  19C14.     On  the  development  and  nature  of  neuroglia.     Am.  Jour.  .Anat.,  vol.  3.  p.  J 
Hardy,   1899.     On  the  structure   of  cell   protoplasm.     Jour,   of  Physiol.,   vol.    14,   p.    187. 
Hober,   1914.  Physikalische  Chemie  der  Zelle  und  der  Gewebe.     Leipzig  and  Berlin,   S.   313. 
Holmgren,    1904.     t'ber   die  Tropospongien   der   Xervenzellen.      .Anatomischer    Anzeiger,    Bd. 

Huntington,  1910.  The  phylogenetic  relations  of  the  lymphatic  and  blood-vascular  systems 
vertebrates  and  the  genetic  principles  of  the  development  of  the   systematic  lymphatic  vessels  in 

Isaacs,   1916.     Properties  of  colloids  in  relation  to  tissue  structure.     Anat.  Rec,  vol.   10,  p.   5 

Isaacs,  1917.  The  reaction  of  the  kidney  colloids  and  its  bearing  on  renal  function.  .■ 
Jour.  Physiol.,  vol.  45,  p.  71. 

Kampmeier,  1912.  The  development  of  the  thoracic  duct  in  the  pig.  .\m.  Jour.  .Knat..  vol. 
p.  430. 

Kaneko,  1904.  Kiinstliche  Erzeugung  von  Margines  falciformes  und  .Arcus  tendinei.  .\rch 
ICntwicklungsm.  Bd.   18,  S.  317. 


92.      Reticulated 


velopment  to  the  connective  tissues  from  the  co 


.\ra.  Jour.  Anat.,  vol.  1,  p.  33 
-Mann,  "'       ■   " 


Physiological    histology,    Oxford,    p.    10<>. 
Maxinow,    1906.     L'ber    die    Zellformen    des    Lockeren    Bindgewebes.      .•\rch.    f. 
tomie,  Bd.  67,   S.  683. 


McClure,   1910.     The  extra-intimal  theory  and  the  development   of  the  mesenteric  lymphatics 
the  domestic  cat.     .Anatomischer  Amzciger,  Bd.  37,  S,  101. 

Meves,  1910.  t'ber  Structur 
Kntstehung  der  Bindgewebstibrille 
Anatomic,  Bd.  71,  S.   149. 

Moody,   1910.     Some  features  of  the  histogenesis  of  the   thyroid  gland  in   the   pig.      Anat.   Rec, 
vol.   4,  p.  429. 

Posner  and  Gies,    1904.     ,\   preliminary   study   of   the   dipestibility   of   connective    tissue    mucoids 
in   pepsin-hydrochloric  acid.      .\m.  Jour.  Physiol.,  vol.   11,   p.   350. 

Ranvier,    1889.     Ouoted    from    Schafer:    Text-book    of   microscopic    anatomy,    Uth    ed..    Lond.ui. 
1912,  p.  117. 

Ross,    1915.     The   trophospongium   of  the   nerve  cell    of   the  crayfish    (Cambarus).      Jour.    Comp. 
Xeur.,  vol.  25,  p.  523. 

Rous  and  Jones,  1916.     A  method  for  obtaining  suspensions  of  living  cells  from  the  fixed  tissues 
and   for   the   plating-out   of   individual   cells.      Jour.    Exp.    Med.,   vol.   23,    p.    549. 

Schafer,    1912.     Text-book   of   microscopic   anatomy,    11th   ed.,   London,    1912,   p.    llo. 

Triepcl,  1911.      Das  Bindgewebe  im  Schwanz  von  Anurenlarvcn.     Arch.  f.   Ent«  icklungmckhanik. 


AN    EXPERIiMENTAL    INVESTIGATION    OF    CERTAIN    FEAT- 
URES OF  THE  PHARMACOLOGICAL  ACTION  OF 
SALVARSAN.* 

r,y  D.  E.  Jackson,   Ph.D.,  M.  D.,  and  G.   Raap,   A.  B.,  A.M. 

Cincinnati. 

In  a  series  of  experiments  performed  at  the  Hygienic  Laboratory  in 
Washington  in  the  year  1918  it  was  shown  by  Jackson  and  Smith*  that  one 
of  the  most  important  and  outstanding  features  of  the  acute  symptoms  •>:' 
poisoning  following  the  intravenous  injection  of  arsphenamine  solutions  in 
(logs  consists  in  the  production  of  a  very  marked  and  prolonged  rise  in  the 
pulmonary  blood  pressure.  This  within  itself  would  perhaps  be  sufficient 
to  account  for  a  part,  if  not  for  all,  of  the  milder  toxic  symptoms  which  are 
occasionally  produced  clinically  by  the  injection  of  arsphenamine.  But  aside 
from  the  pulmonary  vascular  changes,  there  remained  the  possibility  that 
the  dyspnea  and  marked  respiratory  disturbances  which  are  frequently  pres- 
ent during  "nitrilnid  crises"  nf  severe,  acute  arsphenamine  intoxication  might 
be  due  to,  or  associated  with,  a  marked  bronchial  constriction.  This  poin.t 
was  not  investigated  by  Jackson  and  Smith,  although  at  that  time  the  pres- 
ence of  some  such  factor  as  this  was  strongly  suspected,  particularly  on  ac- 
count of  the  analogy  in  action  on  the  bronchioles  which  is  often  exhibited 
among  metallic  salts.  In  the  present  work  we  have  carried  out  some  pre- 
liminary experiments  in  order  to  determine  whether  or  not  any  true  bron- 
chial asthmatic  action  is  produced  by  injections  of  arsphenamine. 

The  solutions  used  by  us  have  been  made  up  from  ."salvarsan"  as  jiro- 
duced  by  the  H.  A.  Metz  Laboratories  in  New  York.  Mr.  Metz  has  very 
kindly  supplied  us  with  a  quantity  of  "salvarsan"  of  lot  No.  H56.  This  was 
a  particularly  good  batch  as  had  been  previously  shown  by  laboratory  tests 
and  by  extensive  clinical  use.  Generally  our  solutions  have  been  made  up 
to  2  per  cent,  strength  of  salvarsan,  and  the  amount  of  alkali  used  mi 
neutralizing  the  dihydrochloride  salt  has  been  sufficient  to  produce  the 
disodium  salt,  and  in  most  instances  a  further  slight  excess  of  alkali  has 
been  added.  In  a  few  cases  we  used  mixtures  of  the  mono-  and  di-sodium 
salts.  Fresh  solutions  were  always  made  up  only  a  few  minutes  before  thev- 
were  injected  into  the  animal. 

Figs.  1,  2,  and  3  show  at  once  the  action  which  salvarsan  has  on  the 
systemic  blood  pressure  (lower  tracing)  and  on  the  bronchial  musculature. 
The  lung  tracings  in  these  experiments  were  made  by  means  of  a  special 
method^  in  which  air  was  intermittently  aspirated  from  the  chest  cavity 
while  the  tracing  was  made  by  a  tambour  connected  with  the  side  tube  of  tho 
tracheal  cannula.    The  dogs  were  pithed  in  each  case.    In  tracing  1  it  is  seen 

•I-rom   Tlif    lumnal    of   Uibu.atory    and   Clinical    Medicine.    October,    19J0. 

•From  the  Jiepaitnient  of  PhannacoloRy  of  the  University  of  Cincinnati  Medical  School  Cin 
cinnati,   Ohio. 

Page   ,.'.;? 


RA.YSOHOFF  MFJfORfAL  VOLUME 


that  20  c.  c.  of  2  per  cent,  salvarsan  solution  injected  into  a  dog  weighin<< 
8.5  kilos  produced  practically  no  effect  at  all  on  the  bronchioles,  either  in 
the  nature  of  contraction  or  dilatation.  Fig.  2  shows  a  moderate  contrac- 
tion of  the  bronchioles  as  indicated  by  the  slight  reduction  in  amplitude  of 
the  respiratory  tracing.  (It  should  be  noted  here  that  the  pulmonary  press- 
ure of  this  animal  undoubtedly  rose  to  a  great  height  following  the  injection 
of  the  salvarsan.)  Near  the  end  of  this  tracing  an  injection  of  4  c.  c.  of 
codeine  sulpliate  (20  milligrams)  was  made.  This  produced  a  marked  con- 
traction of  the  bronchioles  and  was  intended  to  be  a  check  on  the  technic 

Paijc  .'JS 


D.  E.  JACKSON  AND  G.  RAAP 


SI  i 

•i3 
1^ 

r          1 

1 

X           1* 

^#31 

1^.                        E 

Figure  2. 


of  the  experiment  in  order  to  show  that  the  apjiaratus,  the  lungs,  etc.,  were 
all  working  proijerly.  Fig.  3  is  a  similar  experiment  in  which  20  c.  c.  of 
salvarsan  caused  a  slight  dilatation  of  the  bronchioles.  These  experiments 
show  that  good  preparations  of  salvarsan  do  not  cause  a  marked  contrac- 
tion of  the  bronchioles.  But,  on  the  other  hand,  they  do  not  show  that 
especially  toxic  preparations  might  not  produce  very  serious  results  in  this 
direction.  Obviously  this  point  should  be  investigated  further,  and  with  a 
much  larger  range  of  samples  of  arsphenamine  than  we  have  Iiad  at  our 
command  in  the  present  investigations.    A  number  of  intermediary  cheniica! 


RANSOHOFF  MEMORIAL  VOLUME 


jiiiiiiijfiiiiiiiiiiiiiiiiiiiiiiiininHiip""""""'"""^ 


compounds  produced  in  the  manufacture  of  arsphenamine  were  exammed 
by  Jackson  and  Smith,  but  it  appeared  that  none  of  those  examined  at  that 
time  could  be  responsible  for  severe,  acute  symptoms  following  arsphenamme, 
injections.  But  in  a  later  paper  by  Smith''  it  was  shown  that  another  inter- 
mediary compound,  namely  amino-hydroxy-phenyl-arsenoxide.  which  is  an 
oxidation  product  of  arsphenamine,  affected  the  pulmonary  blood  pressure 
in  a  manner  quite  comparable  with  that  of  a  solution  of  arsphenamine  of 
corresponding  strength.     "The  arsenoxide  content  of   arsphenamine  varies 

Page  iV) 


D.  E.  JACKSON  AND  G.  RAAP 


As=0 
NHo 


OH 
usually  between  0.5  and  2  per  cent.     Occasionally  a  preparation  is  encoun- 
tered that  contains  as  high  as  5  per  cent,  arsenoxide    (Dr.  C.   N.   Myers, 
quoted  by  Smith )  and  such  a  prcjiaration  might  very  readily  be  highly  toxic 


Figure  4. 

owing  solely  to  its  arseno.xide  content."  Jn  a  recent  article  by  Schamberg, 
Kolmer  and  Raiziss*  the  jirescnce  in  some  arsphenamine  and  neoarsphen- 
amine  preparations  uf  an  unidentified  toxic  substance  designated  by  them 


RANSOHOFP  MEMORIAL  VOLUME 


as  "X"  has  been  emphasized.  And  Stokes  and  Busman^  have  reported  toxic 
reactions  following  injections  of  arsphenamine  through  a  ^^^t^'"  ^rand  of 
so-called  pure  gum  rubber  tubing  when  this  is  new,  but  not  after  the  tubmg 
has  been  used  for  a  short  while.  It  is  obvious  that  such  factors  as  these 
might  possibly  cause  a  severe,  or  even  fatal,  bronchoconstrict.on  m  very 
susceptible   patients,   when   any    such   constriction   was   complicated  by   th. 


lll^iiiiiiiiiiiiiliiiiiiiiiiiiiHillllliMIIM""'''"''"'' 


simultaneous  presence  of  a  great  rise  in  the  pulmonary  artena  pressure 
Unfortunately  it  will  require  many  more  expermients  before  all  such  ob 
sou  mi  phenomena  as  these  can  be  fully  investigated.  But  the  present  ex- 
perL'nt's  have  been  sufficient  to  show  that  any  dangerous  b-ncoconstr.c- 
tion  is  not  to  be  feared  with  the  proper  use  of  prst-class  prcpa,aUons  o. 
arsphenamine.     (See  also  Hanzlik  and  Karsner^j 

Page  IVi-i 


D.  E.  JACKSON  AND  G.  RAAP 


Bearing  in  mind  the  evident  rise  in  pulmonary  arterial  pressure  after 
arsphenamine  injections,  as  first  demonstrated  by  Jackson  and  Smith/  and 
which  was  further  investigated  by  Smith'*  alone,  we  have  attempted  in  th^ 
present  work  to  investigate  further  certain  features  of  this  important  reac- 
tion. We  have  accordingly  devised  a  very  sensitive  method  for  detecting 
verv  minute  changes  in  the  pulmonary  pressure.     The  arrangement  of  the 


iiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiitiiiiiiiiiniii»iii»iiii""iiii'ii»"imi imiiii 

Figure  6. 
apparatus  as  used  by  us  is  diagrammatically  illustrated  in  Fig.  4.  In  this 
illustration  it  will  be  seen  that  a  cannula  tied  into  the  left  pulmonary  artery 
was  connected  with  a  manometer  by  rubber  tubing.  The  chest  was  opened 
widely  and  artificial  respiration  was  maintained  throughout  the  experiment. 
Ether  was  administered  by  means  of  a  special  sight-feed  device"  which  has 

Page  :.",.; 


RAXSOHOFF  MEMORIAL  VOLUME 


been  described  by  us  elsewliere.  The  manometer  and  the  rubber  tubing  con- 
necting witli  tlie  puhnonary  artery  were  all  filled  with  normal  salt  solution 
(0.8  per  cent,  sodium  chloride  in  water).  This  solution  has  worked  very 
well  for  us,  and  clotting  has  been  very  much  less  troublesome  than  was  the 
case  when  we  used  sodium  citrate  solution.  This  latter  is  very  poisonous 
and  easily  stops  the  heart  if  a  small  amount  gets  back  into  the  right  ven- 
tricle. Sodium  chloride  solution  does  not  afifect  the  heart.  The  top  of  the 
distal  limb  of  the  manometer  was  connected  by  rubber  tubing  to  a  burette 
of  50  c.c.  capacity.  The  salt  solution  reached  only  a  little  way  up  in  the 
burette,  the  upper  part  of  which  contained  air  and  was  connected  by  means 
of  glass  and  rubber  tubing  to  a  tambour  having  a  bowl  about  two  inches  in 
diameter.  The  tambour  was  very  sensitive  and  thus  readily  recorded  on 
the  drum  very  minute  changes  in  the  pulmonary  pressure.  Carotid  pressure 
was  recorded  in  the  usual  manner  with  a  mercury  manometer. 

Fig.  5  shows  the  results  in  two  dififerent  dogs  of  injections  of  salvarsan 
solution,  as  recorded  from  the  pulmonary  (upper)  and  carotid  (lower) 
arteries.  It  will  be  seen  that  the  pulmonary  pressure  rose  abruptly  to  a 
great  height  and  that  it  did  not  fall  until  the  carotid  pressure  reached  a 
very  low  level.  In  the  left  hand  tracing  only  8  c.c.  in  all  was  injected  into 
a  small  dog,  yet  this  killed  the  animal.  In  the  right  hand  tracing  20  c.c.  of 
solution  was  fatal. 

Fig.  6  shows  a  jirofound  and  lasting  rise  in  pulmonary  pressure  follow- 
ing injection  of  20  c.c.  of  2  per  cent,  salvarsan  solution.  It  will  be  noted 
here  that  the  carotid  pressure  remained  at  almost  the  normal  height  for  a 
considerable  time  after  the  injection  of  the  drug,  which  was  carried  out 
rapidly.  And  again  the  pulmonary  pressure  remained  very  high  until  the 
heart  had  reached  an  extremely  weakened  condition. 

From  Figs.  5  and  6  it  will  be  seen  that  sudden  intravenous  injections  of 
.salvarsan  produce  their  chief  circulatory  results  primarily  in  the  limgs. 
■From  a  clinical  standpoint  it  is  interesting  to  speculate  as  to  what  symptoms 
such  an  action  as  this  might  produce  in  the  patient.  And  Fig.  6  shows 
further  that  an  ordinary  blood  pressure  determination  as  recorded  from  the 
arm  might  ])rove  very  deceptive  so  far  as  showing  the  real  condition  of  the 
entire  circulatory  system  was  concerned.  For  here  the  general  systolic 
pressure  had  fallen  only  a  few  millimeters  at  a  time  when  the  pulmonary 
pressure  had  risen  to  an  enormous  height.  It  will  be  noted,  of  course,  that 
the  dose  and  rate  of  injection  here  considerably  exceeded  that  applying  clin- 
ically. We  have  accordingly  attempted  to  get  some  comparative  insight  into 
the  matter  by  giving  very  small,  consecutive  injections  as  shown  in  Fig.  7. 
In  this  case  1  c.c.  was  injected  and  then,  after  an  interval,  a  further  1  c.c. 
etc.,  was  given.  In  this  manner  we  are  able  to  observe  the  immediate  results 
following  each  separate  small  dose.  It  is  seen  that  1  c.c.  causes  a  very  con- 
siderable rise  in  pulmonary  pressure.  The  second  1  c.c.  dose  still  further 
increases  this  rise,  as  does  each  of  the  succeeding  injections.     And  it  will 


D.  E.  JACKSON  AND  G.  RAAP 


be  seen  that  the  systemic  pressure  actually  rose  following  the  first  injection. 
Five  injections  of  1  c.c.  each  and  one  injection  of  3  c.c.  (8  c.c.  in  all)  finally 
brought  the  pulmonary  pressure  almost  to  the  limit  of  its  capacity  to  rise. 
And  this  process  represented  a  duration  of  some  minutes. 

Figs.  5,  6  and  7  all  well  illustrate  a  peculiar  phenomenon  which  appears 
to  be  always  present  in  experiments  involving  the  rapid  injection  of  salvar- 
san  solutions.  It  will  be  noted  that  in  each  of  these  tracings  the  pulmonary 
tambour  at  the  very  beginning  of  the  record  exhibited  marked  excursions 


up  and  down.  These  excursions  resulted  from  the  respn-atory  movements 
of  the  lungs.  The  corresponding  excursions  can  also  be  seen  in  the  mer- 
cury manometer  tracing  from  the  carotid  pressure.  The  speed  of  the  drum 
was  too  slow  here  to  show  the  blood  pressure  movements  following  each 
individual  beat  of  the  heart.  But  immediately  after  the  injection  of  the 
drug  the  pulmonary  pressure  started  to  rise.  At  the  same  time  the  ampli- 
tude of  the  respiratory  excursions  of  the  tambour  began  to  decrease,  and  as 
soon  as  a  very  high  altitude  was  reached  by  the  pressure  tlie  respiratory 

Page  21,5 


RANSOHOFF  MEKWRIALJ^VLUME_ 


excursions  were  reduced  to  a  minimum  or  disappeared  altogether.  But  du  - 
neall  this  period  the  respiratory  inflation  and  deflation  of  U.e  ungs  re- 
main d  consLt.  for  this  was  carried  out  by  means  of  an  art.fic.al  resp.ra- 
doTmachine.  Now  let  us  ask.  What  is  the  cause  of  th,s  pecuhar  change 
"he  pulmonary  blood  pressure  as  reflected  from  the  respiratory  excur- 
sionso?  the  lungs?  For  we  have  noted  above  that  but  httle  change  was 
produced  in  the  bronchial  musculature  by  the  salvarsan. 


Figure  8. 


Fig  8  probably  illustrates  a  point  having  a  bearing  on  this  subject.  In 
this  tracing  it  is  seen  that  three  small  iniections  of  2  -,.-f  P™^"^  .^ 
marked  rise  in  the  pulmonary  pressure  but  had  only  a  shght  e^ect  on  he 
carotid  pressure.  Following  these,  however,  an  mject.on  of  /.  ex.  of  adrena- 
line (1-10,000)  was  given  and  this  raised  the  carotid  pressure  but  marked^ 
lowered  the  pulmonary  pressure.  At  the  same  time  there  was  a  shght 
tendency  for  the  amplitude  of  the  respiratory  movements  of  the  pulmonary 
tambour  to  increase,  that  is,  to  return  toward  the  normal  agam.    But  as  the 

Page  2!fi 


D.  E.  JACKSON  AND  G.  RAAP 


effects  of  the  adrenaline  wore  off  the  respiratory  excursions  of  the  tambour 
again  became  reduced.  This  same  point  is  again  illustrated,  perhaps  more 
markedly,  in  Fig.  9.  This  peculiar  and  unexpected  action  of  adrenaline 
calls  to  mind  at  once  the  various  clinical  recommendations  which  have  been 
made  by  Milian,^  Beeson,"  and  others  regarding  the  use  of  adrenaline  in 
cases  of  severe  arsphenamine  poisoning.  And  the  relation  which  adrenaline 
bears  to  the  spasmodic  contraction  of  the  bronchioles  in  acute  anaphylaxis 


Figure  9. 
also  reminds  one  of  the  various  anaphylactic  hypotheses  by  which  different 
writers  have  attempted  to  explain  the  cause  of  arsphenamine  poisoning.  We 
have  not  been  able  to  prove,  however,  that  the  phenomena  which  we  have 
noted  here  as  being  produced  by  adrenaline  in  cases  of  experimental  acute 
salvarsan  poisoning  bear  any  direct  relation  to  the  clinical  results  which 
have  been  described  as  being  produced  by  adrenaline  injections  in  some  cases 
of  arsphenamine  poisoning.     On  the  other  hand,  the  apparent  improvement 

Page  2J,1 


RANSOHOFF  MFMORIAL  VOLUME 


and  lowering  of  the  pulmonary  pressure  would  undoubtedly  be  ot  beneht  u, 
these  cases  We  strongly  suspect  that  the  lowering  of  the  pulmonary  pres- 
sure here  was  due  to  a  mechanical  shifting  of  the  blood  from  the  venous 
,0  the  arterial  side  of  the  circulatory  system.  This  would  result  from  con- 
traction of  the  arterioles.  The  direct  action  of  adrenaline  on  the  hear 
would  also  tend  to  m^prove  the  general  character  of  the  circulation.  t 
would  appear  that  when  the  pulmonary  pressure  is  verv  lugh.  then  the  pul- 


J^^.Wu^-^'^y^^^ 


m 


iiAij|u|j^i| 


Figure  10. 
monary  arterioles,  etc..  are  put  on  such  a  high  tension  that  the  regular  respir- 
atory movements  of  the  lungs  are  not  sufficient  to  cause  much  change  m  the 
relative  movement  and  volume  of  blood  in  the  pulmonary  vessels,  as  indi- 
cated in  the  tracing  made  by  the  pulmonary  tambour.  Adrenaline  causes 
a  general  shifting  of  the  blood  volume  and  thus  indirectly  affects  the  pul- 
monary pressure. 

We  wish  now  to  take  up  another  phase  of  the  subject.     It  was  long  ago 
shown  by  Joseph"  that  acid  solutions  of  arsphenamine  could  produce  precip- 

Pa«e  218 


D.  E.  JACKSON  AND  G.  RAAP 


itation  in  the  blood  if  the  concentration  of  the  drug  exceeded  0.1  ])er  cent. 
And  Danysz'"  has  attempted  to  show  that  precipitation  of  the  arsphenamine 
occurs  both  in  vitro  and  vivo  even  with  alkaline  solutions.  Smith, ^  in  the 
light  of  these  and  other  previous  observations,  has  carefully  studied  this 
point  with  reference  to  the  action  of  solutions  of  arsphenamine  on  serum 
in  vitro.  He  finds  that  acid  solutions  (dihydrochloride)  of  arsphenamine 
produce  very  bulky  precipitates  in  serum  in  vitro,  and  also  cause  a  great 
rise  in  pulmonary  pressure  if  injected  intravenously.  In  vitro  the  precipi- 
tate between  serum  and  the  monosodium  salt  of  arsphenamine  varies  from 


*                        X                             , 

^d{J.QT^*^ 

^^^^^-^            /-f(y,ooo 

m\\\\\\\\mm\\\im\\m\\\wmm 

v^^^v^v 

^^^^1« 

^■Co^^- 

iiiiiiiimiiimiil 

^ 

Figure  11. 
a  distinct  turbidity  to  a  moderately  heavy  precipitate.  But  Smilh  found  that 
no  precipitate  occurred  in  vitro  between  dog  serum  and  alkaline  arsphena- 
mine solutions  containing  0.8  c.c.  or  more  normal  sodium  hydrate  per  100 
mg.  of  drug.  Smith  has  also  shown  further  that  perfusion  of  the  lungs  with 
a  solution  of  arsphenamine  dihydrochloride  in  physiological  salt  solution 
causes  a  contraction  of  the  pulmonary  vessels  and  a  consequent  decrease  in 
the  rate  of  outflow  of  the  perfusion  fluid.  Since  this  occurs  with  acid 
arsphenamine  solutions,  it  seems  evident  that  the  drug  itself  acts  directly 
on  the  pulmonary  arterioles  to  cause  contraction,  and  that  this  is  not  entirely 
dependent  on  the  alkali  of  the  solutions  as  ordinarily  used.    Apparently  then 


RANSOHOFF  MEMORIAL  VOLUME 


pulmonarv  vascular  obstruction  may  be  due  to  an  extensive  precipitate  of  the 
drug  to  a'specific  action  of  the  drug  itself  on  the  muscle  fibers  of  he  arteriole 
.alls  and  to  the  presence  of  alkali  in  the  solution  used.  In  order  to  throw 
some  further  light  on  this  question  we  have  made  injections  of  the  drug 
into  the  femoral  artery  as  shown  in  Fig.  9.  In  this  case  ,t  will  be  seen  that 
a  dose  of  12  c  c  produced  a  considerable  rise  in  the  pulmonary  pressure. 
(The  rise  was  really  about  twice  as  great  as  the  curve  shows,  for  a  shght 
le-ik  in  the  metal  bowl  of  the  tambour  was  allowing  air  to  escape  very  slowly 
throughout  the  tracing.  This  was  discovered  after  the  experiment  was 
over  )  We  believe  that  in  this  case  the  drug  (injected  into  the  peripheral 
end  of  the  femoral  artery)  simply  washed  out  the  blood  from  the  artery  and 


then  passed  directly  on  into  the  femoral  vein  without  being  precipitated  out 
to  any  marked  extent  in  the  leg  capillaries.  This  then,  was  almost  equivalent 
to  slow  injection  into  the  femoral  vein  directly.  .      .  ,r. 

We  next  proceeded  to  inject  the  salvarsan  solution  into  a  branch  of  the 
portal  vein.  In  this  case  the  solution  had  to  pass  through  the  liver  capil- 
laries as  shown  diagrammatically  in  Fig.  4.  Fig.  10  shows  the  result  ot  two 
uch  injections  (of  5  c.c.  and  7  c.c).    h  will  be  noted  that  no  rise  occurred 


D.  E.  JACKSON  AND  G.  RAAP 


in  the  pulmonary  pressure,  but  on  the  contrary  some  sHght  fall  may  have 
been  produced. 

Fig.  11  shows  first  an  injection  of  5  c.c.  of  salarsan  solution  into  the 
portal  vein  of  a  small  dog.  This  ])roduced  an  obvious  fall  in  both  the  pul- 
monary and  the  carotid  pressures.  Following  this  y>  c.c.  of  adrenaline  solu- 
tion was  given.  This  caused  a  slight  fall  of  pulmonary  pressure,  but  only 
a  faint  rise  of  the  systemic  pressure.  As  a  check  on  the  action  of  the  ap- 
paratus, etc.,  two  other  injections  (3  c.c.  and  10  c.c.)  of  salvarsan  solution 
were  finally  given  by  way  of  the  femoral  vein.  The  latter  of  these  produced 
a  very  obvious  rise  in  the  pulmonary  pressure.  These  experiments  evidently 
show  that  the  liver  has  removed  from  the  salvarsan  solution  its  power 
to  cause  a  rise  in  the  pulmonary  pressure.  But  on  the  contrary  some  por- 
tion of  the  drug  must  pass  through  the  liver  and  on  into  the  general  circu- 
lation, for  Fig.  11  shows  that  the  salvarsan  injections  caused  the  systemic 
pressure  to  fall  to  zero  and  thus  caused  the  death  of  the  animal.  This  same 
point  is  further  illustrated  in  Fig.  12.  Here  40  c.c.  of  1  ])er  cent,  salvarsan 
solution  was  injected  (between  the  points  marked  x,  x).  This  dose  by 
femoral  vein  would  certainly  have  raised  the  pulmonary  pressure  to  a  great 
height.  Here,  however,  only  a  gentle  rise  in  the  pulmonary  pressure  was 
produced,  and  this  appears  as  if  it  might  have  been  due  simply  to  the  addi- 
tion of  solution  to  the  blood  volume  of  the  animal.  But  nevertheless,  tliis 
dose  of  the  drug  still  exercised  a  very  obvious  toxic  action  on  the  animal. 
Near  the  end  of  the  tracing  an  attempt  was  made  to  inject  salvarsan  into 
the  femoral  vein.  Three  and  one-half  c.c.  were  injected  which  started  to 
produce  an  immediate  rise  in  the  pulmonary  pressure,  but  unfortunately 
some  air  passed  into  the  vein  through  the  injecting  cannula  and  the  animal 
died  of  air  embolism  (verified  at  autopsy).  The  marked  rise  in  the  ]nil- 
monary  tambour  here,  however,  serves  as  a  valuable  check  on  the  technic 
of  the  experiment  and  shows  that  any  rise  which  the  salvarsan  might  have 
produced  in  the  pulmonary  pressure  would  have  been  promptly  recorded. 
We  feel  obliged  to  conclude,  therefore,  that  if  salvarsan  solutions  be  injected 
into  the  portal  vein,  the  passage  of  the  drug  through  the  liver  will  almost, 
if  not  totally,  remove  its  power  to  raise  the  pulmonary  pressure.  It  is  prob- 
able that  this  action  occurs  to  some  extent,  and  this  may  be  rather  marked 
in  some  instances,  in  the  case  of  the  arterioles  and  capillaries  of  the  leg 
also.  But  the  liver  seems  to  be  much  more  effective  in  this  direction  than  are 
the  tissues  of  the  leg. 

It  seems  probable  to  us  that  this  action  of  the  liver  results  mainly,  if  not 
entirely,  from  a  precipitation  of  the  major  portion  of  the  salvarsan  within 
the  organ  itself,  perhaps  in  the  form  of  emboli  in  the  liver  capillaries.  The 
well-known  detoxicating  action  which  the  liver  manifests  toward  manv 
poisons  is  not  probably  extensively  concerned  in  this  matter,  at  least  not  in 
the  manner  in  which  such  detoxication  is  usually  considered.  There  is  a 
rather  striking  significance  in  the  rapidity  with  which  this  precipitation  must 

Page  2r,l 


RAXSOHOFf  MEMORIAL  VOLUME 


occur  in  the  liver,  if  this  i>  the  correct  explanation,  for  evidently  only  a  very 
small  proportion  of  the  pulmonary  pressure  raising  substance  passes  the 
liver,  while  at  the  same  time  very  obvious  effects  from  the  drug  may  be 
IJroduced  in  the  carotid  pressure  immediately.  This  point  perhaps  has  a 
bearing  on  the  marked  symptoms  of  liver  disturbance,  jaundice,  etc..  which 
are  frequently  manifested  clinically  in  arsphenamine  poisoning. 

CONCLUSION'S. 

1.  First-class  preparations  of  salvarsan  have  almost  no  direct  action  on 
the  bronchial  musculature  of  the  dog.  It  seems  obvious  that  acute  symp- 
toms resembling  anaphylactic  shock,  or  the  so-called  "nitritoid  crises,"  if 
produced  by  good  preparations  of  salvarsan  cannot  be  due  to  a  spasmodic 
contraction  of  the  bronchioles.  But  we  are  not  sure  that  this  action  might 
not  occur  in  the  case  of  esi^ecially  toxic  samples  of  the  drug. 

2.  We  have  studied  the  action  of  salvarsan  on  the  pulmonary  pressure 
by  means  of  an  especially  sensitive  method.  We  believe  that  even  the 
smallest  injections  of  salva'-san  exercise  some  immediate  action  on  the  pul- 
monary pressure.  Its  detection  depends  only  on  the  sensitivity  of  the  method 
employed  for  its  investigation. 

?i.  When  the  ptilmonary  pressure  has  l>een  greatly  raised  by  salvarsan 
we  have  noted  that  injections  of  adrenaline  tended  to  lower  this  pressure, 
and  also  to  restore  the  excursions  of  the  pulmonary  pressure  due  to  the 
respiratory  movements  of  the  lungs,  when  these  had  been  previously  greatly 
reduced  by  the  salvarsan.  We  believe  this  results  mainly  from  a  mechanical 
shifting  of  the  blood  from  the  action  of  the  adrenaline  on  the  systemic 
vasculature. 

4.  When  solutions  of  salvarsan  are  injected  into  the  general  circulation 
by  way  of  the  femoral  artery  the  ])ulmonary  blood  i)ressure  is  still  raised 
by  the  drug.  But  the  rise  in  pressure  is  less  than  if  the  drug  were  injected 
by  the  femoral  vein. 

5.  When  solutions  of  salvarsan  are  injected  into  the  portal  vein  and  are 
thus  carried  through  the  liver  before  ])assing  into  the  general  circulation, 
then  it  is  found  that  the  drug  produces  but  little  if  any  effect  on  pulmonary 
pressure,  although  if  the  dosage  is  very  large  the  pulmonary  pressure  may 
be  raised  slightly,  apparently  only  as  the  result  of  an  increased  volume  of 
fluid  in  the  vessels.  But  toxic  doses  thus  injected  tend  to  lower  the  pul- 
monary pressure. 

6.  We  believe  this  action  of  the  liver  is  brought  about  by  a  precipitation 
of  the  drug  in  the  capillaries  and  arterioles  of  the  liver.  This  apparently 
does  not  correspond  to  the  ordinary  detoxicating  action  of  the  liver  as  mani- 
fested on  many  poisons. 

7.  This  precipitation  in  the  liver  takes  place  quickly  and  it  does  not  pre- 
vent some  portion  of  the  drug  from  passing  on  into  the  general  circulation. 


D.  E.  JACKSON  AND  G.  RAAP 


For  the  systemic  pressure  may  fall  to  a  proportionately  much  j^^reater  degree 
than  does  the  pulmonary  pressure. 

REFKRKNCUS. 

1.  Jackson.   1).    !■:..  ami  Sniitii,   JI.   I.:     Jour.   Pharmacol,  and  Kxper.   Therap.,   1918,   xii.  221. 

2.  Jackson,  1).  K. :  Jour.  Pharmacol,  and  Kxper.  Therap.,  1914,  vi,  57.  Experimental  Phar- 
inacology,    1918,   C.    \'.   iMosby  Co.,    St.    Louis,   p.   287. 

3.  Smith,    M.    I.:      Jour.    Pharmacol,    and    E.xper..    Thfra]).,     1920,    .xv,    279. 

4.  Schamberg,  J.  F.,  Kolmer,  J.  A.,  and  R.i,.,~  ,  . :  W  \,n  ]..u,  Med.  Sc,  1920,  clx.  No. 
2,  p.  188.  See  also  Kaiziss,  G.  W.,  and  Proskf.m  '  '  i  ,  i  ,,t  .\rsphenamine  and  Its 
Relation  to  Toxicity,  Arch.  Dermat.  and  Syph.,  ]'.■  r  i  l..,hiur,  J.,  and  Lucke,  1!.: 
Pathologic  Changes  after  Arjphenamine  and  Nm  ,  ;  s'l  Koth.  C.  B. :  Tox- 
icity of  Arsephenamine  and  Neo-arspbenamine,  ibi'i  ,  i'  J''  st.k-.,  I  H  :  Therapeutics  of  Ar- 
sephenamine,  ibid.,  p.  .^M.  Stetson,  D.  D. :  Permanent  Solution  of  Arsphenamine.  ibid.,  p  324 
Hanzlik,  P.  J.,  and  Karsner,  H,  T. :  Jour.  Pharmac.  and  Exper.  Therap.,  1919,  xiv,  p.  425;  ibid., 
1919,  xiv,  p.   375. 

5.  Stokes,  J.  H.,  and  Busman,  C.  J.:     Jour.  Am.  Med.  Assn.,  1920,  Ixxiv,  No.   15,  p.   1013. 

6.  Jour.    Lab.   and   Clin.    Med.,    1920,   v,    745. 

7.  Milian:  Les  intolerants  du  606;  Bull.  Soc.  franc,  de  dermat.  et  syph,  1913,  xxiii  5 '0 
L'administration   de  I'adrenaline.     Paris   Med.,    1918,  2   fevrier. 

8.  Becson,    B.    B.:      Am.  Jour.    Syph.,    1919,    iii,    p.    129. 

9.  Joseph,   I).   R.:     Jour.   Exper.  Med.,   1911,   xiv,  83;   ibid.,   p.    179. 

10.  Danysz:      Ann.    de   ITnst,    Pasteur,    Paris,    1917,    No.    3,    p.    114. 


A  CASE  OF  CANCER  OF  THE  \AGINA.  CERMX  AND  BODY  OF 
THE  UTERIS  TREATED  V,\  RADIUM. 

HowAui.  A.  Kixi.v 


Even  in  these  days  of  easy  and  constant  connnunication.  when  our  tens 
of  thousands  of  Aescula]iians  have  one  and  all  become  devotees  of  the  peri- 
patetic philosopher,  surgery  still  advances  as  heretofore  through  the  ideas 
developed  in  sundry  pregnant  centers  where  dwells  the  great  man.  From 
the  time  of  Joseph  Ransohoff's  activities  from  the  earl\  eighties  on.  Cincin- 
nati has  been  recognized  as  one  of  these  fruitful  centers,  a  source  of  emana- 
tions of  great  ideas  in  the  surgical  field.  His  work  is  especially  characterized 
by  its  catholicity,  embracing  as  it  has  gynecology — see  his  paper  on  "Two 
ovariotomies  in  the  same  patient"  (1885) — his  work  on  the  anatomy  oi  the 
cecum  and  appendix  (1888).  when  appendicitis  was  just  beginning  to  attract 
attention;  his  brain  surgery,  his  hernia  work,  his  gall-stone  o[ierations.  and 


;rapli  sliovving  tissue  rciiK.v.il  l,y  ciiicttemetit  of  ult-nis  licfore 
ratlimii  tri'atinciit.     .\.  indicates  invasion  of  epithelioma  into  uterine  wall. 

above  all.  what  attracted  my  own  attention  the  most,  liis  splendid  contribu- 
tions to  the  surgery  of  the  kidney,  when  that  important  organ  was  still  a 
terra  incognita  for  the  average  surgeon. 

Aside  froiu  his  distinguished  and  widely  recognized  (|ualities  as  a 
surgeon.  Dr.  Ransohofif  was  one  of  the  ])ioneers  of  this  country  in  the  recog- 
nition of  the  value  of  radium  as  a  therapeutic  agent,  either  co-operative  with 
surgery  or  substituting  it  or  yet  again  operative  in  cases  where  surgery  is 
impotent.  .A  large  e.xperience  thus  enabled  him  soon  to  lay  down  the  rules 
of  dosage  and  a])])lication  so  difficult  in  this  new  field,  where  so  much  danger 
lurks  in  overdosage.    I  refer  particularly  to  such  publications  as : 

Page  .'.J( 


HOWARD  A.  KELLY 


Radium  Treatnient  (jf  Cancer  (with  J.  L.  Ransohofif),  Lancet-Clinic, 
111,  661  (1914). 

Radium  Treatment  with  L'terine  Cancers  (with  J.  L.  Ransohoff),  Ann. 
of  Surg..  64,  298  (VnG)  ;  Trans.  Am.  Surg.  Assn..  ,54.  202  (1916). 

Radium  Treatment  of  L'terine  Fibroids,  Lancet-Clinic,  115,  116  (1916). 

The  following  case  illustrative  of  an  extensive  cancer  of  the  cervix, 
uterus  and  vagina,  with  the  sketches  and  sections  made  in  the  cour.se  of  the 
treatnient  and  progress  towards  recovery,  is  reported  as  one  of  the  inter- 
esting and  remarkable  examples  of  the  potency  of  this  newest  and  most 


\o.  2.  Photomicrograph  showing^  tissue  removed  liy  ciirettemenl  ten  weeks  after 
radium  treatment.  The  hyaline  tissue  is  typical  and  follows  lieavy  radiation.  Note 
complete  absence  of  epithelium  and  the  thick  wall  of  the  blood  vessel  in  the  upper  left 
hand  portion  in  the  midst  of  the  hyaline  tissue  glands. 

wonderful  of  all  our  remedies,  in  the  field  which  Dr.  Ransohoff  has  culti- 
vated with  such  assiduity  and  success. 

The  patient,  J.  H.  M.,  No.  5902,  a  woman  56  years  old,  consulted  me  January  2(1, 
1920,  complaining  of  bloody  vaginal  discharge,  pain  in  the  back,  pelvis  and  linilis.  loss 
of  weight  and  bladder  irritability. 

Her  family  history  was  negative.  Past  history  :  Health  always  good  :  no  serious 
illnesses;  no  operations;  menstrual  history  normal;  menopause  at  48  with  no  symp- 
toms.    Marital  history:     Five  children,  all  spontaneous  deliveries. 

Present  illness  ;  In  the  spring  of  1917  patient  noticed  a  slight  intermittent  leucor- 
rhea  which  gave  her  no  particular  trouble  until  April,  1919,  when  it  became  constant 
and  at  times  blood-tinged.  This  became  more  profuse,  and  from  .August,  1919,  on,  it 
was  bloody.  In  November,  1919,  she  began  having  pain  in  her  back,  radiating  into  the 
pelvis  and  limbs,  .^bout  the  same  time  she  noticed  bladder  irritability  with  constant 
desire  to  void.    For  the  past  three  or  four  months  there  has  been  progressive  weakness. 

General  physical  examination  negative  except  for  some  pallor  and  evidence  of 
recent  loss  of  weight.     No  enlarged  lymphatic  glands  anywhere. 

Pelvic  examination :  Vagina  short ;  pronounced  rectocele ;  cervix  at  first  touch 
appears  normal,  but  on  closer  examination  it  is  softish  and  nodular,  the  anterior  lip 
more  involved  than  the  posterior — the  anterior  lip  is  fused  with  the  anterior  vaginal 
wall  and  there  is  a  submucous  thickening  extending  from  the  junction  of  the  cervix  and 
anterior  wall  to  the  orihce  of  the  urethra.  The  uterine  body  is  somewhat  enlarged; 
there  is  no  evidence  of  lateral  disease,  or  thickening  in  either  broad  ligament.     On  with- 

Pagc  .:.;s 


RAX  so  H  OFF  MEMORIAL  VOLUME 


drawing  the  gloved  hand  there  is  quite  a  little  bloody  discharge.  -Inspection  in  the 
knee-chest  posture  shows  a  submucous  thickening  extending  over  the  anterior  lip  of  the 
cervix  down  on  to  the  vaginal  wall.  There  are  several  little  granular  areas  which  bleed 
easily  on  touch.  Protruding  from  the  cervical  canal  there  is  a  fringe  of  friable  tissue. 
Examination  under  anesthesia  confirmed  without  adding  to  the  above  findings.  Dila- 
tation and  curettage  showed  a  cervix  enlarged,  easily  dilated,  filled  with  friable  tissue 
which,  when  curetted,  leaves  a  crater.  The  body  of  the  uterus  was  packed  with  the 
same  friable  tissue.  Tissue  from  both  cervix  and  body  of  uterus  showed  a  basal  cell 
epithelioma. 

Treatment :  On  account  of  the  extensive  local  uterine  involvement  and  the  definite 
extension  over  the  entire  anterior  vaginal  wall,  radium  was  advised  in  preference  to 
operation. 

On  January  30,  1920,  she  was  given  1208  millicuries  screened  with  2  mms.  of  brass 
and  1  mm.  of  rubber  for  three  hours  and  forty  minutes— three-fourths  of  the  treat- 
ment distributed   on   three  areas   in   uterine  cavitv   and   one-fourth   in   cervical   canal. 


Xo.  3.  Photomicrograph  showing  tissue  removed  by  curettemeiit  nine  months 
after  radium  treatment.  This  shows  the  end  result  following  radiation.  Note  the 
fibrous  tissue  and  the  distended  glands. 

Patient  was  a  little  nauseated  from  the  treatment,  but  no  mure  upset  than  she  was 
following  the  dilatation  and  curettage.     She  returned  home  on  February  2. 

She  came  back  on  .April  15.  1920.  .-Ml  of  the  bloody  discharge  had  stopped  the 
second  week  in  February.  Since  then  there  has  been  a  scanty,  serous  discharge.  She 
has  had  no  pain,  and  has  gained  several  pounds  in  weight,  and  appears  to  be  in  splendid 
health  and  is  stronger — in  fact,  she  has  none  of  her  former  symptoms. 

\  pelvic  examination  showed  the  cervix  contracted,  perfectly  normal,  absolutely 
freely  movable  in  every  direction — uterine  body  upright,  a  little  enlarged  but  perfectly 
freely  movable.  There  was  a  slight  bloody  discharge  after  examination.  Inspection 
showed  the  cervix  normal.  The  anterior  vaginal  wall  was  also  normal,  and  palpation 
shows  no  extension  on  the  anterior  vaginal  wall.  Curettage  of  the  uterine  cavity 
obtained  a  little  necrotic  tissue,  the  curet  quickly  reaching  a  firm,  fibrous,  grating  base. 
Microscopic  examination  of  tissue  showed  hyalinized  fibrous  tissue  with  no  epithelial 
cells. 

On  September  24,  1920,  patient  had  gained  in  weight,  strength  and  in  every  way. 
Has  had  a  troublesome  leucorrhea  for  the  past  two  months,  but  no  bleeding.  Has  been 
having  some  neuritis  in  limbs  and  is  neurotic  and  apprehensive. 

Pelvic  examination  shows  vagina  negative  as  to  any  evidence  of  disease.  Cervix 
normal,  senile,  atrophic.  Uterus  upright,  not  definitely  enlarged.  In  contact  with  the 
vagina  there  is  a  sensation  of  resistance  posterior  on  the  right.  Per  rectum  this  thick- 
ening is  definitely  felt  with  the  finger,  but  it  is  more  like  that  which  is  due  to  simple 
lack  of  flexibility  of  the  tissues  rather  than  disease.  There  is  no  evidence  of  meta- 
stasis in  iliac  or  inguinal  glands.     On   dilatation  there  is  a  discharge  of  pus  and  on 

Page  SSe 


HOWARD  A.  KELLY 


curettement  a  necrotic  material  (pyomctra)  is  obtained — curctteinent  quickly  readied 
a  firm,  muscular  base.  Curettings  examined  microscopically  showed  only  radiated 
tissue. 

After  this  examination  was  completed  and  the  patient  was  reassured  that  there 
was  absolutely  no  evidence  of  the  old  trouble,  she  was  much  relieved  and  during  the 
rest  of  her  stay  sutTered  little  from  the  neuritis  which  she  complained  of  at  home. 


Note. — All  these  slides  were  made  immediately  a 
sections  stained  with  hematoxylin  and  eosin.  It  is  of 
satisfactory  slide  records  can  be  made  in  this  way,  t 
delay.  This  method  of  immediate  examination  eman; 
worked  out  by  Dr.  Thos.  S.  Cullen.  It  has  now  been 
It  is,  however,  not  generally  known  that  it  obviates,  ir 


the  time  of  the  examination,  and  are  frozen 
reat  importance  to  know  that  permanent  and 
us  saving  much  laboratory  labor  as  well  as 
:ed  from  my  laboratory,  where  it  was  first 
'idely  adopted  in  Europe  as  well  as  at  home, 
many  cases,  further  section  cutting,  as  here. 

Page  ?.57 


THE  DIAGNOSIS  AND  TREATMENT  OF  DIAPHRACxMATIC 
PLEURISY:    WITH  REPORT  OF  CASES.* 

By  T.  H.  Kellv.  B.  S..  M.  D.. 

ami 

H.  B.  Weiss.  A.  B..  M.  D. 

Cincinnati. 

For  many  years  it  has  been  noted  that  not  infrequently  a  pneiinionia 
begins  with  symptoms  resembhng  acute  abdominal  disease,  particularly  in 
children.  J.  P.  Crozer  Griffith'  reported  several  cases,  as  did  also  Herrick- 
and  others.  Needless  to  say.  many  clinicians  have  suffered  the  experience 
of  advising  operation  for  some  acute  intra-abdominal  condition,  only  to  find 
the  abdominal  contents  normal  and  a  pneumonia  in  one  of  the  patient's  lower 
lobes  the  day  following  the  operation. 

To  Capps^  we  owe  the  well-defined  picture  of  invohenient  of  the  dia- 
phragm by  inflammatory  processes.  He  published  in  191 1  the  results  of 
experimental  irritation  of  the  diaphragmatic  pleura  in  a  series  of  human 
beings,  the  work  being  done  upon  patients  with  pleural  effusions.  Irritation 
of  the  diaphragm  was  accomplished  by  means  of  a  wire  introduced  through 
a  trocar  inserted  into  the  pleural  cavity  preparatory  to  the  withdrawal  of  the 
pleural  effusion.  His  observations  covered  experiments  upon  seventy-five 
patients,  only  thirty-five  of  whom  presented  favorable  conditions  for  free 
exploration  of  the  diaphragm.  He  also  presented  in  the  paper  a  very  com- 
plete discussion  of  the  previous  work,  which  has  been  published  upon  the 
innervation  of  the  visceral  and  parietal  pleura. 

He  concluded  from  his  experiments  that : 

1.  The  visceral  pleura  is  not  endowed  with  pain  ^ense. 

2.  The  parietal  pleura  is  richly  supplied  with  sensory  fibers  from  the 
intercostal  nerves  and  irritation  of  it  produces  pain  that  is  accurately  local- 
ized by  the  individual  over  the  spot  that  is  touched.  Such  irritation  never 
gives  rise  to  "referred"  pain  in  the  neck  or  elsewhere. 

3.  The  diaphragmatic  pleura  receives  its  nerve  supply  from  the  last  six 
intercostal  nerves,  which  supply  a  peripheral  rim  of  the  diaphragm  two  or 
three  inches  wide  anteriorly  and  laterally  and  a  segment  corresponding  to 
the  posterior  third,  and  from  the  phrenic  nerve  which  supplies  the  central 
portion  of  the  diaphragmatic  pleura. 

The  pain  produced  by  irritation  of  the  central  part  of  the  diaphragmatic 
pleura  is  a  true  referred  pain,  and  is  distributed  over  the  skin  and  tissues 
supplied  by  the  third  and  fourth  cervical  segments,  with  a  predilection  for 
the  trapezius  ridge. 

The  pain  elicited  by  irritation  of  the  peripheral  or  posterior  jiortion  of 
the  diaphragmatic  pleura  is  also  a  true  "referred"  pain.    The  pain  is  usually 

•From  The  .American  Journal  of  the  Medical   Sciences,  December,   1918.     From  the  Department 
of  Internal  Medicine.  University  of  Cincinnati,  the  Medical  Clinic  of  the  Cincinnati  General  Hospital 
and  the  Wi'helra  and  Gette  Beckman  Dispensary. 
Page  258 


T.  H.  KELLY  AND  H.  B.  WEISS 

distributed  in  segmenta  areas  over  the  lower  thorax  and  epigastrium,  some- 
times extending  downward  over  the  whole  abdomen  on  the  same  side  (sev- 
enth to  twelfth  dorsal  segments). 

Both  pains  are  spontaneous  and  are  associated  with  hyperesthesia  and 
hyperalgesia  of  the  skin  and  superficial  tissues  on  pressure. 

4.  The  pericardial  pleura  receives  its  innervation  chiefly,  if  not  exclu- 
sively, from  the  phrenic  nerve.  Irritation  of  this  part  of  the  pleura  results 
in  "referred"  pain  in  the  neck  of  the  same  character  as  that  following  irri- 
tation of  the  central  portion  of  the  diaphragmatic  pleura. 

This  work  offered  a  definite  starting-point  from  which  to  work  in  the 
diagnosis  of  involvements  of  the  diaphragmatic  pleurae,  and  in  1916  Capp^' 
published  a  series  of  sixty-one  cases  of  diaphragmatic  pleurisy,  in  all  of 
which  the  diagnosis  was  confirmed  either  by  autopsy  or  the  subsequent  his- 
tory of  the  cases.  In  this  article  he  called  attention  to  the  various  distribu- 
tions of  the  referred  abdominal  pain,  and  emphasized  the  points  of  ditifer- 
cnce  between  it  and  the  pain  of  true  abdominal  disease. 

The  skill  and  muscles  of  the  abdomen  are  more  sensitive  in  referred  pain 
from  the  diaphragmatic  pleura  than  in  abdominal  visceral  disease,  and  the 
cutaneous  reflexes  are  more  lively  in  referred  pain.  Deep  pressure  with  the 
flat  hand  is  better  born  in  referred  diaphragmatic  pain,  while  it  produces 
deep  pain  over  an  inflamed  organ  within  the  abdomen. 

The  presence  of  sharp  localized  pain  in  the  neck,  occuring  spontaneously 
or  only  on  pressure,  on  the  same  side  as  the  abdominal  pain  often  suggests 
the  true  state  of  aiifairs,  as  it  indicates  irritation  of  the  phrenic  nerve.  The 
referred  pains  in  the  neck  and  abdomen  are  often  aggravated  by  cough  or 
deep  breathing. 

Also,  in  acute  diaphragmatic  disease  there  are  usually  present  evidences 
of  respiratory  infection,  such  as  cough,  expectoration,  herpes  labialis,  rapid 
respiration,  high  leukocytosis,  etc.  According  to  Capps,  hiccough  is  not 
common  in  diaphragmatic  disease,  as  was  formerly  supposed,  having  oc- 
curred only  five  times  in  his  sixty-one  cases. 

The  differential  diagnosis  of  involvement  of  the  diaphragmatic  pleura 
and  abdominal  disease  is  very  important,  and  at  times  the  clinician  is  in  a 
veritable  whirlpool  of  indecision  concerning  the  correct  diagnosis.  We  have 
had  the  opportunity  in  the  past  two  years  of  observing  in  the  Cincinnati  Gen- 
eral Hospital  and  the  Wilhelm  and  Gette  Beckman  Dispensary  a  number  of 
patients  exhibiting  some  or  all  of  the  features  mentioned  by  Capps  in  his 
dscription  of  diaphragmatic  pleurisy.  In  certain  of  these  cases  the  question 
of  surgical  intervention  was  quite  acute  and  the  importance  of  correct  diag- 
nosis therefore  correspondingly  great. 

From  these  cases  we  have  selected  twenty-two  in  which  the  diagnosis 
was  confirmed  either  by  their  future  course  or  at  the  autopsy  table,  and  are 
presenting  them,  hoping  to  show  the  variations  in  the  manifestations  of 
diaphragmatic  pleural  disease  and  the  different  paths  by  which  we  arrived 

Page  ..'.;;» 


RANSOM  OFF  MEMORIAL  VOLUME 


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r.  H.  KELLY  AND  H.  B.  VVFJSS 


at  a  diagnosis  in  the  different  instances.  The  table  on  page  4  shows  the 
symptoms,  both  subjectixe  and  (ilijective,  that  were  found  in  onr  cases. 
(See  Fig.s.  1,  2,  .1) 


Fig.  1,  Ca.se  1.     Showing  points  of  tendcrnL-ss  along  the  trapezius  and  beneath  the 
twelfth  rib  posteriorly. 

Of  these  twenty-two  cases,  ten  were  acute  in  cliaracter,  three  had  acute 
exacerbation  at  the  time  of  observation  and  nine  were  subacute  or  chronic. 
The  following  cases  in  the  first  group  resembled  surgical  conditions  so 
closely  that  the  question  of  operati\e  intervention  was  seriously  considered : 


l'"ig.  2,  Case  2.     Showing  points  of  tenderness  along  the  trapezius,  in  solid  marking,  and 
the  stippling  showing  areas  of  hyperesthesia  and  hyperalgesia. 

No.  1,  renal  stone;  No.  4,  acute  cholecystitis;  No.  6,  cholelithiasis  with 
colic;  No.  8.  generalized  acute  peritonitis  from  perforated  typhoid  ulcer; 
No.  14,  operation  was  done  for  an  acute  appendicitis,  much  to  our  chagrin  ; 
Nos.   18  and  22  both  had  operation   for  gall-bladder  disease  several  years 


RANSOHOFF  MEMORIAL  VOLUME 


previous  to  the  time  of  obserxation.  In  both  cases  neither  stones  nor  any 
other  pathological  condition  were  found  at  operation,  and  shortly  afterward 
there  was  a  recurrence  of  the  symptoms  that  had  existed  before  the  opera- 


Fig  3,  Case  3.  Showing  points  of  tenderness  along  the  trapezius  posteriorly  and 
tenderness  heneath  the  twelfth  rih  and  an  area  of  hyperesthesia  over  the  fourth  dorsal 
spinous  process. 


Fig.  4,  Case  12.    .\  lateral  view  showing  areas  of  hyperesthesia  and  points  of  tenderness 
along  the  trapezius  and  beneath  the  twelfth  rib  posteriorly. 


tion.     In  the  remaining  cases  of  the  acute  group  the  symptoms  or  history 
immediately  gave  an  inkling  as  to  where  the  seat  of  the  trouble  lay. 

In  the  group  of  chronic  types  the  question  of  surgical  treatment  arose 
in  No.  7,  which  is  interesting  because  it  combined  definite  symptoms  of  dia- 
phragmatic pleurisy  and  a  chronic  appendicitis,  which  were  both  proved  by 
the  further  history  of  the  case.    In  the  acute  cases  the  symptoms  arose  sudi 


T.  H.  KELLY  AND  H.  R.  WEISS 


denly,  as  with  the  onset  of  pneumonia,  and  after  several  weeks  practically 
all  the  symptoms  had  left.  On  the  other  hand,  in  the  chronic  cases,  the  onset 
was  acute  and  the  symptoms  subsided,  but  at  irregular  intervals  there  was  a 
recurrence  of  the  symptoms,  in  whole  or  in  part,  usually  without  an  increase 
in  temperature  and  not  with  the  original  acuteness.  At  these  periods  of 
recurrence  exertion  and  cough  intensified  the  symptoms,  and  frequently 
exertion  was  the  cause  of  the  recurring  attack.     The  chronic  sutYerers  com- 


Fig.  6,  Cast-  1.     Sliuwing  a  definite  area  of  infiltration  six  days  after  the  first  picture 
was  taken. 

Paul'   'M3 


RAXSOHOPF  MEMORIAL  VOLUME 


jilained  just  as  biitcrly  of  the  pain  and,  occasionally,  of  the  hyperesthesia  as 
those  who  suilered  from  an  acute  attack. 

Hyperalgesia  and  hyperesthesia  were  not  always  marked,  being  present 
in  seven  cases.     The  hyperesthesia,  when  present,  was  most  acute,  and  one 


Fig.  7,  Case  6.  Showing  the  position  of  the  diaphragm  and  markings  of  the  right 
lower  base.  One  month  alter  this  plate  was  taken  another  pair  of  stereoscopic  plates 
"failed  to  show  the  shadows  at  the  right  base  which  were  seen  on  the  previous  plates." 


Fig.  8,  Case  1.3.     Showing  di 


diaphragm  liv  adhcsii 


of  the  patients  cried  out  when  the  tips  of  the  fingers  were  passed  over  the 
skin.  In  one  patient  clothing  was  almost  unbearable.  The  involvement  in 
hyperesthesia  was  usually  over  a  large  area.  (See  charts.)  Hyperthesia 
Page  nei 


T.  H.  KELLY  AND  H.  B.  IVFJSS 


and  hyperalgesia  were  nuicli  more  apiJarent  in  the  acute  than  in  tlie  clironic 
cases  as  a  rule.  In  the  great  majority  of  cases  deep  abdominal  pressure 
was  borne  quite  well.  Spontaneous  pain  was  not  always  present  in  the  neck- 
when  pain  on  pressure  was  marked. 

The  two  most  constant  areas  of  tenderness  on  ])ressure  were  below  the 
twelfth  rib  posteriorly  on  the  afTected  side  and  at  the  ridge  of  the  trapezius, 
though  the  patients  did  not  always  complain  of  spontaneous  pain  at  these 
points.  The  upper  quadrants  of  the  abdomen  were  the  most  frequent  sites 
of  the  referred  abdominal  pain.  In  many  of  the  cases  the  abdominal  pain 
radiated  toward  the  flanks,  and  in  two  of  them  there  was  definite  tenderness, 
involving  the. entire  half  of  the  back  from  the  lower  ribs  to  the  ilium.  There 
was  usually  moderate  rigidity  and  muscle  spasm  of  the  abdominal  mus- 
cles at  the  areas  of  referred  pain.  Abdominal  symptoms  of  varying  degree 
were  present  in  nineteen  of  the  twenty-two  cases.  In  two  cases  there  wa> 
board-like  rigidity  over  the  abdomen.  One  was  oj)erated  for  relief  of  acute 
appendicitis  and  the  appendix  was  found  apparently  imiocent  of  any  dis- 
ease. In  the  other  case  (No.  8)  the  rigidity  and  muscle  spasm  continued 
until  there  appeared  definite  signs  of  consolidation  in  the  left  base.  This 
is  the  only  patient  who  died,  and  at  autopsy  the  pathologist  reported:  "In 
the  left  pleural  cavity  there  were  a  few  acute  fibrinous  adhesions  over  the 
left  lower  lobe  and  no  fluid.  The  pleural  surface  of  the  left  side  of  the 
diaphragm  was  congested  and  had  about  its  middle  point  and  extending  pos- 
teriorly from  this  a  small  amount  of  fibrin,  some  of  which  was  undergoing 
organization.  Beneath  this  and  surrounding  it  there  was  exceedingly  well- 
marked  venous  congestion.  The  peritoneal  surface  of  the  diaphragm  showed 
nothing  but  slight  congestion.  The  lower  lobe  of  the  left  lung  showed  a 
diffuse  lobar  consolidation,  and  all  of  the  bronchi  of  this  lobe  were  filled  with 
pus.    There  were  no  abnormal  findings  in  the  abdomen." 

Capps  states  that  in  his  series  of  sixty-five  cases  hiccough  appeared  in 
only  five  cases,  while  in  our  twenty-two  cases  this  symptom  occurrt>d  in  two 
cases,  and  in  both  was  quite  intractable,  all  of  the  usual  methods  for  its  relief 
failing,  the  hiccoughs  apparently  ceasing  spontaneously. 

Fourteen  of  our  cases  were  males  and  eight  were  females.  C.astric 
symptoms  were  not  frequent.  One  case  showed  both  nausea  and  \-omiting, 
while  nausea  and  vomiting  were  present,  each  once,  in  separate  cases.  In 
seven  cases  friction  sounds  were  heard,  prjictically  all  in  the  lower  axillary 
region  of  the  affected  side.  These  friction  sounds  were  probably  due  to  an 
associated  involvement  of  the  costal  pleura.  Five  patients  had  pneumonia 
associated  with  their  pleurisy.  In  the  majority  of  the  acute  cases  there  was 
a  rise  in  temperature,  though  not  very  high.  The  leukocyte  count  was  in- 
creased, depending  on  the  acuity  of  the  symptoms  as  a  rule ;  associated  with 
the  increase  in  leukocytes  there  was  a  proportionate  rise  in  the  polymor- 
phonuclear neutrophile  cell  count. 


RANSOHOFF  MFMORIAL  VOLUME 


In  but  four  of  the  nineteen  cases  examined  by  the  Roentgen  rays  there 
were  no  findings  suggestive  of  pleural  or  pulmonary  involvement.  The 
Roentgen-ray  finding  varied,  ranging  from  definite  distortion  of  the  dia- 
phragmatic contours  to  merely  a  definite  increase  of  the  hilum  markings 
radiating  to  the  border  of  the  diaphragm.  In  several  instances,  shadows 
suggesting  calcification  were  lying  close  to  the  diaphragm.  In  two  of  the 
accompanying  reproductions  of  Roentgen-ray  plates  one  can  see  in  the  early 
picture  a  finger-like  infiltration  above  the  diaphragm  and  in  the  latter  picture 
the  shadow  of  a  definite  infiltration  of  the  lung  in  the  same  region. 

The  diagnosis  of  diaphragmatic  pleurisy  was  usually  made  on  the  occur- 
rence of  pain  in  the  side,  associated  with  pain  beneath  the  twelfth  rib  on  the 
affected  side  and  along  the  edge  of  the  trapezius  on  that  side.  The  jiain  may 
be  spontaneous  in  the  neck  and  was  so  in  one-third  of  our  cases.  In  nine- 
teen out  of  twenty-two  cases  there  was  tenderness  along  the  edge  of  the 
trapezius.  There  is  almost  a  constant  finding  of  tenderness  on  pressure 
beneath  the  twelfth  rib  posteriorly  on  the  affected  side ;  this  symptom  was 
present  nineteen  times  in  twenty-two  cases.  In  the  vast  majority  of  the 
cases  there  is  referred  pain  in  the  abdomen,  with  varying  degrees  of  muscle 
spasm  and  rigidity.  A  moderate  rise  in  temperature  with  an  increase  in  the 
leukocytes  and  polymorphonuclear  cells  is  usually  jiresent.  In  some  cases 
there  are  heart  friction  sounds  in  the  lower  axilla. 

The  Roentgen-ray  examination  of  the  chest  in  over  three-fourths  of  the 
cases  did  shorv  definite  diaphragmatic  involvement  or  pulmonary  involve- 
ment close  to  the  diaphragm. 

In  chronic  cases  there  is  exacerbation  of  the  characteristic  symptoms  on 
exertion,  cough  and  frequently  on  deep  inspiration. 

Treatment.  In  the  acute  cases  the  treatment  is  that  of  any  pleuritis.  We 
have  found  that  cold  applications,  in  the  form  of  iced-linen  strips,  applied 
(and  frequently  changed)  to  the  aiifected  side  for  two  hours,  is  most  effica- 
cious. Of  course,  sedatives  are  used  when  necessary.  Strapping  the  lower 
chest  and  upper  abdomen  seems  to  give  the  greatest  relief,  and  man\  of  our 
chronic  cases  return  to  us  asking  that  their  sides  be  strapped.  They  have 
found  that  after  the  side  has  been  strapped  their  pains  will  be  relies  ed  almost 
immediately  and  that  they  will  be  free  from  their  annoying  sym])toms  for 
from  several  weeks  to  months. 

We  are  indebted  to  Mr.  R.  Isaacs  for  the  accompanying  charts. 


BIBLIOr.R.AiPHV 

Griffith:      Toiu 

.    .Am.   Med.   Assn..    190.1.  xi.  .S.ll. 

Herrick:     Jou 

r.    Am.    Med.    Assn.,    1903,  xi,   535. 

Capps:     .Arch. 

Int.   Med.,   1911.  No.  6.  viii,  /l/. 

Capps:     .Am. 

lotir.  Med.  Sc.  1916.  No,  3.  cM.  33.1 

DEMONSTRATION    OF    THE    INTERVENTRICULAR    MUSCLE 
BANDS  OF  THE  ADULT  HUMAN  HEART.* 

By  H.  McE.  Knovver 

Cincinnati. 

This  demonstration  is  made  on  a  specimen  of  adult  human  heart  in  which 
the  fat,  coronary  vessels  and  epicardium  have  been  removed  to  expose  the 
superficial  muscle  fibers  of  the  ventricles  and  of  the  conus.  This  super- 
ficial sheet  is  cut  on  the  posterior  surface  to  the  left  of  the  posterior  inter- 
ventricular groove  (sulcus  longitudinalis  posterior),  and  the  right  ventricle 
rolled  away  from  the  left  after  the  method  followed  by  J.  B.  Macallum  with 
pig  embryos'  hearts.  The  septum  is  thus  split  open,  exposing  the  inner 
terminations  of  the  muscle  bands  which  arise  superficially  from  the  right 
and  left  atrio-ventricular  rings,  and  from  the  conus,  and  end  in  the  papillary 
muscles  of  the  left  ventricle.  Deeper  fibers  are  also  shown,  extending  from 
the  left  ring  to  the  large  papillary  mu.scle  of  the  right  ventricle,  and  from 
the  conus  to  this  papillary  muscle.  The  membranaceous  septum  is  split, 
showing  the  position  of  the  atrio-ventricular  bundle  of  His  in  a  novel  and 
striking  manner.  The  septal  blood-vessels  are  also  found  readily.  The 
right  and  left  ventricles  may  be  thus  unrolled  furthej  until  opened  from  the 
septal  side,  as  done  by  Macallum  for  young  pig  hearts.  A  fair  proportion 
of  hearts  taken  from  dissecting-room  subjects,  preserved  by  injection  of  car- 
bolic, glycerin,  alcohol  solution  and  afterward  kept  for  a  time  in  cold  storage 
or  in  vats  of  weak  carbolic,  are  found  to  be  suitably  macerated  for  this 
demonstration. 

The  results  of  Winkler,  Pettigrew,  Ludwig,  Krehl  and  Macallum  are 
thus  readily  examined  in  the  human  heart ;  we  believe  for  the  first  time. 

It  is  urged  that  students  should  be  induced  to  .study  the  heart  in  this 
way,  after  working  out  the  coronary  circulation,  etc.,  rather  than  to  simply 
cut  open  the  ventricles  after  the  method  used  by  the  pathologist  in  autopsy, 
since  these  cuts  destroy  the  important  muscle  connections.  The  tracing  of 
the  muscle  bands  between  the  right  and  left  ventricles  will  furnish  a  valuable 
aid  to  the  better  appreciation  of  the  action  of  the  heart.  The  relations  of 
the  papillary  muscles  to  the  interventricular  (and  conus)  muscle  bands  can 
hardly  be  understood  without  this  dissection. 

The  study  has  since  been  confirmed  and  e.xtended  by  F.  P.  Mall,  1911.  in  his  Muscular  Archi- 
tecture of  the  Ventricles  of  the  Human  Heart,  .Vmerican  Journal  of  Analomy,  Vol.  H.  p.  2IJ,  etc.; 
also,  by  J.  Tandler,   1913,   in   his  Anatomic  des  Herzens,   Vienna,   p.    171. 


the  proceedings  of  the  .Amer 


OCL'LAR  AXGIO-SCLEROSIS.* 

r.y  GicoKci.;  H.  Kkkss.  R.  S..  M.  D. 

Los   Angeles. 

THE  TERM   AXGIO-SCLEROSIS. 

Ocular  angio-sclerosis.  as  a  term  to  indicate  the  hardening  or  over- 
growth of  connective  tissue  of  the  walls  of  the  blood-vessels  of  the  eye,  is 
perhaps  a  better  term  under  which  to  group  the  type  of  changes  to  be  here 
discussed,  than  to  refer  to  the  process  either  as  arterio-  or  phlebo-sclerosis, 
although  it  must  be  confessed  that  the  term  arterio-sclerosis.  through  com- 
mon usage,  conjures  up  the  most  definite  conception  to  the  minds  of  many 
of  us. 

The  study  of  sclerosis  of  the  vascular  system  is  especially  interesting  to 
ophthalmologists,  because  in  the  eye,  as  nowhere  else  in  the  body,  do  we  find 
an  organ  with  terminal  arteries  where  many  of  the  changes  in  the  structure 
of  the  blood-vessels  can  be  thoroughly  examined  from  day  to  day. 

VASCULAR  SCLEROSIS  CLOSELY  ASSOCL\TED  WITH  FAULTS  OF  OUR 
CIVILIZATIOX. 

The  close  association  of  sclerosis  of  the  vascular  system  with  some  of 
the  major  faults  and  vices  of  our  civilization,  such  as  over-eating,  high  ten- 
sion living  (both  mental  and  physical),  alcoholism,  and  syphilis;  and  its 
intimate  connection  with  chronic  nephritis  (perhaps  as  often  a  percursor 
as  a  corollary  of  the  last-named  disease)  ;  as  well  as  with  the  fault  of  simple 
old  age  (a  condition  most  of  us  aspire  to  in  spite  of  its  defects  and  disad- 
vantages), even  though  we  are  less  disposed  to  accept  that  of  our  heredity,  a 
causative  factor  also  to  be  reckoned  with ;  and  the  further  fact  that  vascular 
sclerosis  more  often  manifests  itself  after  the  age  of  forty,  at  which  time 
most  persons  have  occasion  to  seek  the  services  of  an  oculist ;  and  that  a 
careful  examination  of  the  fundus  at  that  period  may  give  important  data 
at  just  the  time  when  there  may  be  few  other  clinical  symptoms  of  arterio- 
sclerosis elsewhere,  should  make  this  subject  one  of  equal  and  nf  \ery  con 
siderable  interest  to  eye  specialists  and  to  general  practitioners  alike. 

AXGIO-SCLEROSIS  A  GRAXE  DISEASE. 
General  arterio-sclerosis  is  a  condition  not  to  be  permitted  to  go  on  to 
terminal  or  very  frank  stages,  if  health  and  life  are  to  be  conserved ;  and 
ocular  angio-sclerosis,  not  alone  because  of  its  capacity  to  impair  vision,  but 
because  the  changes  of  the  sclerotic  process  are  in  the  eye  sometimes  earlier 
or  more  evident  than  in  other  portions  of  the  body,  can  therefore,  be  the 
means  of  earlier  diagnosis  and  proper  treatment;  and  through  its  early 
recognition  we  may  be  in  a  position  to  prolong  the  life  of  a  considerable 
number  of  our  patients. 


•From   The    Ophthalmoscope,    December, 
Page  268 


GEORGE  H.  KRESS 


OCULAR  ANGIO-SCLEROSIS  FREQUENT  PAST  THE  AGE  OF  FORTY. 
Hirschberg.  in  a  series  of  cases  of  old  persons  coming  to  him  for  refrac- 
tion, found  evidence  of  retinal  angio-sclerosis  in  50  per  cent.,  and  micro- 
scopic examinations  of  the  retinal  vessels  of  old  people  show,  according  fo 
Hertel,  an  even  higher  percentage  of  sclerotic  invohenient  than  this. 

HYPERTEXSiOX   A   FREOUENT  CONCOMIT.KNT  OF  ANGIO-SCLEROSTS : 

AND   THE   NEED   OF   DETERMINING  WHETHER 

HYPERTENSION  EXISTS. 

Since  the  sclerotic  changes  are  so  often  a.^^^ociated  with  hypertension  of 
the  vascular  system,  the  question  suggests  itself  as  to  whether  it  should  not 
be  a  routine  practice  for  eye  specialists  to  take  the  blood  pressure  of  all 
patients  seeking  refraction  about  the  age  of  forty  and  after ;  to  the  end  that 
a  special  effort  may  be  made  to  obtain  an  exact  record  of  the  condition  of 
the  ocular  vascular  system  in  such  persons  as  give  evidence  of  increased 
blood  i)ressure.  The  fact  that  an  increased  general  blood  pressure  so  dis- 
covered may  also  enable  us  the  better  to  guard  against  glaucoma,  is  likewise 
important  to  eye  specialists. 

Increased  vascular  blood  pressure  has  also  been  noted  in  connection  with 
cataract,  and  even  though  it  is  not  possible  to  stop  this  lens  change,  appro- 
priate treatment  may,  before  cataract  extraction,  somewhat  reduce  the  dan 
ger  of  post-operative  hemorrhage. 

The  fact  that  it  is  still  a  matter  of  discussion  as  to  whether  vascular 
hypertension  is  or  is  not  antecedent  to  vascular  sclerotic  changes,  need  not 
concern  us,  since  we  are  in  possession  of  the  important  fact  that  nearly 
always  this  hypertension  is  one  of  the  early  manifestations  or  concomitants 
of  vascular  sclerosis ;  although  it  must  be  remembered  that  there  be  those 
who  believe  that  in  this  early  stage,  a  hypotension  may  alternate  with  a 
hypertension  (the  latter  construed  to  be  dependent  at  this  stage  upon  a 
spasm  of  the  muscular  coats  of  the  arteries). 

IXTRA-OCULAR  GLOBE  TENSION  MIGHT  ALSO  WELL  BE  TAKEN. 

In  taking  these  blood  pressure  readings,  it  might  well  be  a  part  of  our 
routine  to  take  also  a  reading  of  the  intra-ocular  globe  tension  with  a  Schiotz 
tonometer  or  a  Gradle  or  other  modification.  The  tonometer  (using  1  per 
cent,  holocain,  which  is  slightly  antiseptic,  and  which  does  not  exfoliate  the 
corneal  epithelium,  as  does  cocaine,  to  anesthetize  the  cornea)  can  be  quickly 
used;  and  the  information  received  from  such  a  tonometer  reading  is  gen- 
erally conceded  to  be  far  more  accurate  and  valuable  th;in  that  from  linger 
palpation. 

THE  NOR.^L\L  AN.\TO.\lV  OF  THE  RETINAL  BLOOD-VESSELS. 
According  to  Oalman.  in  the  large  central  artery  of  the  optic  nerve, 
there  can  be  deiuonstrated  an  outer   (adventitial    of   coimective  tissue;  a 
middle    (or  media)    of   elastic  and   fibrous   tis-,ue.   interspersed  with   a   few 


RAXSOHOFF  MEMORIAL  VOLUME 


muscle  elements:  and  an  innter  (or  intima)  made  up  of  ( 1  )  an  elastic 
lamina;  (2)  a  subendothelial  layer,  and  (3)  a  stratum  of  endotlielial  cells. 
As  the  central  artery  appears  on  the  disc,  however,  and  its  branches  get 
farther  away  therefrom,  the  above-mentioned  subendothelial  layer  and  elas- 
tic layer  of  the  intima  usually  give  place  to  a  few  elastic  fibres  only. 

.\s  regards  the  normal  veins,  however,  in  the  retinal  divisions  uf  the  nor- 
mal central  vein,  this  subendothelial  layer,  and  the  so-called  elastic  membrane 
of  the  intima.  are  lacking;  and  the  retinal  veins  are.  in  fact,  little  more  than 
tubes  of  fibrous  tissue  lined  by  endothelial  cells. 

THE  MORBID  AX.ATOMV  OF  THE  RETINAL  BLOOD-VESSELS. 

It  is  not  necessary  for  our  purpose  to  go  into  much  discussion  concerning 
the  microscopic  morbid  anatomy  of  the  sclerosed  blood-vessels  other  than 
to  reiterate  that  in  the  arteries,  the  inner  coat  shows  a  thickening,  either 
from  patchlike  areas  of  endothelial  proliferation,  or  from  a  very  consid- 
erable addition  to  the  subnedothelial  connective  tissue  (the  latter  more  of  a 
fibrosis,  and  then  process  most  often  met  with  in  the  veins)  ;  the  middle  coat 
presenting  usually  areas  of  necrosis  and  hyaline  and  fatty  degeneration,  with 
formation  of  atheromatous  detritus,  which  may  or  may  not  be  later  on  infil- 
trated with  calcareous  material.  The  outer  coat  in  more  advanced  cases 
may  also  show  thickening,  but  whether  this  is  due  to  the  circulating  to.xins 
or  is  only  an  evidence  of  compensatory  thickening  or  protection  of  the  ves- 
sel wall,  is  not  yet  determined. 

In  phlebo-sclerosis.  the  intima  likewise  shows  the  increase  of  connective 
tissue  in  the  internal  coat,  and  the  degenerative  changes  in  the  outer  layers, 
with  a  weakening  and  widening  thereof,  or  if  calcareous  dejiosits  be  asso- 
ciated, then  a  stiffening  or  hardening  of  the  vessel. 

These  facts  concerning  the  normal  and  abnormal  anatomy  of  the  retinal 
blood-vessels  should  be  borne  in  mind  in  any  consideration  of  the  changes 
which  take  place  in  ocular  angio-sclerosis. 

HOW  THE  IXTERXAL  EYE  TUNICS  SUEEER  THRt)LC.H 
ANGIO-SCLEROSIS. 

.A.S  a  result  of  the  angio-sclerotic  changes,  the  eye  tunics  are  supplied  by 
blood-vessels  with  narrowed  lumina  and  bathed  with  blood  containing  the 
toxic  elements  lying  at  the  root  of  the  sclerosis.  Consequently,  the  nutrition 
and  metabolism  of  the  retinal  and  other  ocular  tissues  sutYers.  Associated 
with  the  above  factors  are  the  weakened  vessel  walls  and  their  greater  tend- 
ency to  leak  and  be  responsible  for  hemorrhagic  spots  in  the  retina. 

THE  EFFECTS  OE  ANGIO-SCLEROSIS  ON  VISION. 

Sudden   diminution   of   vision   of    marked   amount   does   not.   however, 

usually  result  from  angio-.sclerosis,  except  when  the  sclerotic  changes  occlude 

the  lumen  of  the  central  artery  or  vein ;  or,  with  more  extensive  weakening 

of  the  ocular  vessels,  are  responsible  for  a  sudden  intra-ocular  hemorrhage. 


GEORGE  H.  KRESS 


A  weakness  in  the  visual  power  in  persons  ])ast  fort)-,  whicli  does  not 
respond  to  suitable  refractive  correction,  should,  howexer,  lead  to  a  suspi- 
cion of  vascular  changes,  and  indicate  a  close  examination  of  the  retinal 
vessels  to  see  if  such  changes  can  be  discovered. 

SYSTEMIC  SIGXS  OF  ANGIO  SCLEROSIS  ALSO  WORTHY  OF  NOTE. 

In  these  patients  in  whom  arterio-sclerosis  is  suspected,  it  is  well  also  to 
have  the  blood  pressure  taken,  and  the  heart  examined  to  determine  whether 
a  hypertrophied  left  ventricle  is  associated  with  accentuation  of  the  aortic 
second  sound,  or  increased  intensity  of  the  first  sound,  or  whether  there  is 
any  displacement  of  the  apex  beat.  A  careful  and  periodical  examination  of 
the  urine  should  also  be  made. 

If  the  picture  of  retinal  angio-sclerosis  be  at  all  advanced,  even  though 
the  general  signs  of  arterio-sclerosis,  be  not  prominent,  the  possibility  of 
concurrent  cerebral  arterio-sclerosis,  with  its  danger  of  apoplexy,  should  he 
kept  in  mind. 

CLINICAL  STAGES  OF  SYSTEMIC  AXGIO-SCLEROSIS. 
Just  as  in  tuberculosis  we  deal  with  three  stages  of  incipient,  interme- 
diate, and  terminal  involvement,  so  also  in  vascular  sclerosis  do  we  find  a 
beginning  stage,  difiticult  of  recognition;  an  intermediate  stage,  with  franker 
signs ;  and  a  terminal  stage,  in  which  the  involvement  is  so  general  as  to 
nullify  much  of  our  attempted  therapy.  It  is  in  this  third  or  last  stage  also 
that  patients  are  seen  in  whom  a  steadfast  hypo-  may  succeed  a  previously 
persistent  hypertension. 

PECULIARITIES  OF  THE  EYE  STRUCTURE  I.\   RELATION   TO  OCULAR 
ANGIO-SCLEROSIS. 

Without  further  comment,  we  can  now  pass  on  to  a  consideration  of 
ocular  angio-sclerosis  proper,  simply  again  calling  attention  to  the  fact  that 
in  the  eye,  we  are  dealing  with  terminal  or  end  arteries  of  very  delicate  struc- 
ture, with  little  or  no  arrangement  for  compensatory  circulation  (although 
with  the  retinal  veins  there  is  more  provision  for  a  collateral  circulation), 
so  that  endovascular  irritants  have  full  opportunity  to  make  their  power  felt ; 
and,  further,  that  because  of  the  structure  of  the  eye,  we  can  use  our  dark 
room  instruments  in  making  close  and  .systematic  observation  of  these 
changes,  the  handicap  being  not  always  that  the  changes  are  not  present,  but 
that  in  our  haste  we  fail  to  note  them. 

SUBJECTIVE  MANIFESTATIONS  OF  OCULAR  ANGIO-SCLEROSIS. 

Among  subjective  phenomena  may  be  noted  early  decrease  in  the  powej 
of  accommodation,  or  severe  headache  persisting  after  refraction  has  been 
corrected  at  the  onset  of  presbyopia.  The  subject  of  diminution  of  vision 
has  alreadv  been  discussed. 


RAXSOHOFF  MEMORIAL  VOLUME 


OBJECrn-E  SIGXS   OF  OCULAR  ARTERIO-SCLEROSIS. 

Among  the  objective  niaiiifestntidiis  arc  the  fnllowing : 
neneral :    Arcus  senilis  : 

Slow  reaction  of  the  pupil : 

Hyperfemic  optic  disc  of  dull-red  color : 

CEdema  of  the  retina  (patches  more  often  in  the  vicinity  of 

the  disc  or  blood-vessels). 

Course  of  arteries:  a  tendency  to  cork->cre\v  course  in  one  or  more 
arteries,  especially  the  smaller  arteries  and  veins  near  the  disc. 

Number  of  arteries :  a  seeming  increase  in  the  number  of  smaller  retinal 
vessels,  due  to  dilatation  making  them  visible  to  the  eye. 

Pressure  effects  of  arteries:  a  disposition  on  the  |>art  of  the  harder 
arteries  to  flatten  out  the  veins  somewhat,  at  the  places  where  the  arteries 
cross  the  veins ;  or  it  may  be  that  the  course  of  the  vein  at  such  a  crossing, 
where  it  can  ordinarily  be  traced  beneath  the  artery  without  loss  of  con- 
tinuity, is  lost  until  it  reappears  on  the  other  side  of  the  artery. 

Light  streaks  on  arteries :  an  increase  in  the  brightness  of  the  light 
streak  (the  so-called  "silver  wire"  appearance).  Other  streaks  on  arteries: 
with  perhaps  an  associated  continuous,  or  interrupted  and  somewhat  nodular 
whitish  streak  of  lesser  brightness  outside  the  vessel  walls  (this  appearance 
being  in  the  retinal  peripheral  vessels  in  contrast  to  the  occasionally  seen 
congenital  connective  tissue  sheath  of  vessels  which  is  limited  largely  to  the 
disc  area),  these  perivascular  streaks  being  due  to  an  infiltration  in  the 
lymph  sheaths  of  the  vessels,  or  to  the  fact  that  the  usually  transparent 
vessel  walls  in  their  now  thickened  state  reflect  more  light  from  the  blood 
stream  than  formerly. 

Color  and  translucenc\  ot  arteries:  a  decrease  in  the  color  and  tran-- 
lucency  of  the  vessel  walls. 

Locomotion  pulse:  with  these  changes  may  be  present  the  so-called 
"locomotion,"  or  arterial  pulse,  not  dependent  upon  pressure,  as  in  gloucoma. 
Such  a  pulse  is  often  best  seen  where  the  arteries  bend  sharply. 

Venous  pulsation :  in  advanced  retinal  arterio-sclerosis,  because  of  the 
hardened  blood-vessels,  digital  pressure  on  the  eyeball  may  fail  to  bring  out 
venous  pulsation  or  blanching  of  the  vessels. 

Calibre  of  arteries:  while  the  arteries  are  not  often  widened  in  the 
earlier  stages  of  retinal  arterio-sclerosis,  later  on  they  may  become  narrowed. 
The  larger  arteries.  f)r  \eins.  of  the  optic  disc  at  times  show  some  of  these 
changes  best. 

Disc  margin  ajjpearance ;  in  addition  to  the  above,  the  optic  disc  and  the 
larger  retinal  vessels  may  be  surrounded  by  a  greyish  haze. 

Hemorrhagic  spots :  where  the  disease  has  made  greater  progress,  blood 
extravasation  may  occur  near  the  vessels,  ranging  from  dots  and  short 
streaks  to  real  blotches  of  hemorrhage. 

Page  272 


GEORGE  H.  KRESS 


OCULAR   ANGIO-SCLEROSIS   A    DISEASE   AFFECTING   BOTH   ARTERIES 

AND  VEINS;  AND  FURTHER  SIGNS  IN  RELATION  TO 

SOME  OF  THE  PHLEBO-SCLEROTIC  CHANGES. 

The  changes  noted  above  may  not  only  involve  veins  as  well  as  arteries, 
but  also,  to  a  certain  extent,  may  be  almost  limited  to  the  veins.  This  seem- 
ingly larger  involvement  of  the  veins  in  ocular  than  in  general  vascular 
sclerosis,  may  be  explained  in  part  perhaps  because  in  the  eye  we  can  watch 
minute  changes  in  the  vein,  size,  course,  etc.,  which  because  of  less  firm 
anatomical  structures  than  the  arteries,  are  less  discernable  through  coarse 
finger  palpation,  etc.,  in  other  portions  of  the  body. 

In  the  veins,  also,  there  may  be  the  picture  of  constriction  and  dilatation 
in  dififerent  portions  of  the  same  vein. 

If  a  hardened  artery  press  firmly  on  a  vein  beneath,  there  may  be  dila- 
tation in  the  portion  of  the  vein  in  the  periphery  of  the  fundus;  while  the 
part  next  to  the  disc  is  narrowed.  The  pressure  of  the  artery  helps  the 
tendency  toward  the  phlebitis,  wiiich  is  already  present  as  a  result  of  the 
basic  causes  of  the  angio-sclerosis. 

If  the  vein  walls  weaken  only  in  spots,  then  in  lesser  degree,  the  veins 
may  show  the  bulbous  varicosities  seen  in  other  parts  of  the  body. 

With  more  advanced  phlebities,  and  the  secondary  constriction  of  the 
vein  lumen,  spots  of  adjacent  hemorrhage  appear  often  also. 

BOTH  INTRA-  AND  EXTRA-OCULAR  HEMORRHAGES  OF  SIGXH-TCAXCE 
AS  REGARDS  ANGIO-SCLEROSIS. 
In  connection  with  retinal  hemorrhage,  it  is  well  to  remember  that  in 
intra-ocular  blood  extravasation  that  cannot  be  otherwise  accounted  for, 
occuring  in  jjersons  about  the  age  of  forty  or  after,  such  a  sign  should  always 
suggest  thorough  examination  of  the  blood  pressure  of  the  individual.  To  a 
certain  extent,  this  same  suggestion  applies  to  so-called  idiopathic  subcon- 
junctival hemorrhage  and  oedema  of  the  lids. 

AX  EARLY   RECUGXITIOX   OF  OCULAR  AXGIO-SCLEROSIS   IS   VERY 
IMPORTAXT. 

These,  then,  are  some  of  the  signs  of  angio-sclerosis  as  seen  in  the  eye, 
and  as  stated  in  the  beginning,  the  gravity  of  the  general  disease  process,  and 
the  necessity  of  an  early  recognition  and  treatment  thereof,  warrant  a 
close  examination  for  such  changes  in  the  fundi  of  all  persons  coming  to  us 
for  refraction  about  or  after  the  age  of  forty.  By  so  doing,  in  a  consid- 
erable number  of  instances,  it  will  be  possible  to  conserve  the  health  and 
prolong  the  life  of  patients  wiio  themselves  are  altogether  unconscious  of 
the  serious  malady  at  work  within  their  bodies. 

A  I'EW  WORDS  OX  TRKATMEXT. 
In  closing,  a  lew  words  in  regard  to  treatment  may  not  be  amiss.     The 
early  detection  of  vascular  sclerosis  is,  of  course,  of  great  importance,  be- 

Papc  27.; 


RAXSOIfOFF  MEMORIAL  VOLUME 


cause  then  the  cause  can  be  sought  and  an  attempt  made  to  prevent  its 
further  action. 

The  very  nature  of  the  disease,  from  the  standpoint  of  causative  factors 
and  pathology,  necessitates  emphasis  on  the  hygiene  of  h'ving.  The  life 
which  is  indicated  to  be  led  by  such  patients  should  be  one  of  moderation 
in  work,  in  eating,  in  exercise,  and  in  personal  habits  of  life;  with  emphasis 
on  elimination  by  bowels,  kidneys,  skin,  and  respiratory  tracts. 

Proper  drugs  have  their  place,  especially  the  iodides  for  their  alterative 
and  resorptive  effects,  while  symptomatically  the  nitrites  and  sedatives,  like 
the  bromides,  may  be  of  value.  The  digitalis  and  strychnine  groups  can 
also  be  called  upon  if  the  heart  condition  indicates  their  exhibition. 

But  in  any  rational  therapy,  the  elimination  of  the  underlying  causes  of 
the  sclerosis  are,  of  course,  of  the  greatest  importance,  and  in  conjunction 
with  the  above  measures,  cannot  be  too  much  emphasized. 


BIOLOGIC  ASPECTS  OF  DEMENTIA  PR.ECOX.* 
F.  V\'.  Langdon.  M.  n. 

Cincinnati. 

When  the  penius  of  Kraepelin — genius  heing  here,  as  usual,  simply  a 
synonym  for  a  high  order  of  painstaking  work — "merged,"  under  one  name. 
a  group  of  psychoses  characterized  in  common,  by  development  in  adol- 
escence, emotional  apathy,  poverty  of  thought,  inadequacy  of  volition,  and 
progressive  or  intermittent  deterioration,  he  conferred  a  lasting  benefit  on 
the  student  of  mental  disorders  and  the  sociologist. 

This  "master  stroke  of  a  master  mind."  however,  did  much  more  than 
furnish  a  convenient  formula  for  diagnosis  and  prognosis ;  it  suggested  at 
once  the  possibility  of  a  common  cause  or  causes  for  the  disease  process ; 
and  presented  for  solution  the  problems  of  its  possible  biologic  significance 
and  pathologic  interpretation. 

In  brief,  what  does  it  mean  in  terms  of  normal  and  perverted  life? 

These  deeper  problems  are  not  only  important — they  are  of  I'ital  iinpor- 
tance — to  the  civilized  nations  of  the  earth  as  well  as  to  such  as  may  attain 
civilization  in  the  future.  Their  consideration  therefore  is  timely,  partic- 
ularly to  us  of  the  United  States  of  .Atnerica.  the  "melting  pot  of  the  nations." 
where  "preparedness"  is  the  watchword,  and  may  be  the  price  of  continued 
liberty  of.  and  government  by,  the  people. 

To  illustrate  this  point  of  view,  we  have  only  to  realize  that  one-fifth  of 
the  total  discharges  from  our  army  in  1912  was  for  mental  disease  (not 
including  neurasthenia  and  hysteria).  "The  discharge  rate  for  mental  dis- 
ease per  1000  was  2.64 ;  higher  than  for  any  other  class  of  disease ;  tuber- 
culosis, including  all  its  forms,  being  next  with  a  rate  of  1.56  per  1000."' 

The  same  writer  states  that  "more  than  half  the  mental  diseases  with 
which  we  meet  in  the  United  States  Army,  requiring  asylum  treatment,  are 
of  the  one  form,  dementia  prsecox." 

Now.  if  our  present  army,  composed  of  picked  material  of  a  "good" 
physical  and  mental  standard,  develops  2.64  per  1000  of  cases  of  mental  dis- 
ease per  year,  what  may  we  expect  of  the  "1,610,600  men  available  for  mili- 
tary duty,"  in  the  state  of  New  York  for  instance,  according  to  the  report  of 
the  adjutant  general  of  New  York  in  1915?'  Were  these  organized  into  a 
military  body,  the  number  "weeded  out"  in  one  year  on  account  of  mental 
disease,  based  on  the  above  figures,  would  be  4250;  more  than  four  full 
regiments  "killed"  without  firing  a  shot ;  and  of  these  more  than  tivo  whole 
regiments  would  be  victims  of  dementia  prsecox. 

It  is  evident  that  these  figures,  based  on  a  proportion  of  50  per  cent,  of 
dementia  pr?ecox  in  admissions  from  the  army,  to  the  Government  Hospital 
for  the  Insane,  are  higher  than  those  of  the  general  population,  which  range 


RANSOHOFF  MEMORIAL  VOLUME 


from  15  to  25  per  cent,  in  different  states.  liut  it  nnist  be  remembered  that 
the  army  is  recruited  from  "picked"  material  as  regards  age  as  well  as 
physique  and  mentality,  and  consequently  consists  of  men  of  a  "dementia 
prpecox  age,"  in  much  greater  proportion  than  does  the  civil  population. 

There  is  no  reason  to  bcheve  that  the  situation  in  Eurojiean  armies  is 
any  better — if  as  good. 

It  is  not  only  the  material  for  armies  that  is  invoked  in  the  question  of 
dementia  pr.TCox,  but  the  general  population  at  a  most  productive  time  of 
life. 

It  must  not  be  supposed,  however,  that  we  of  the  United  States  of  Amer- 
ica are  alone  in  facing  this  problem.  Our  friend  and  fellow-member  of  this 
association,  Dr.  Frederick  Peterson^'  of  New  York,  writes  me:  "Dementia 
prrecox  is  probably  as  common  in  Japan  as  elsewhere."  This  opinion  is  based 
on  his  own  extensive  observations  in  that  country.  He  also  writes  me  :* 
"I  saw  cases  of  dementia  prsecox  among  the  native  Fellaheen  in  Egypt.  .  .  . 
I  remember  perfectly  a  typical  case  in  a  Sudanese  negress." 


H     I!     Sto.liUit  ) 

Fig.  1.  Chimpanzee:  Hand  showmg  flat  thenar  emnience  and  ['ad  of  thumb 
directed  forward.     (Compare  Fig.  4.) 

My  friend  Dr.  S.  Lilienstein, '  of  r>ad  Nenheini,  German,  a  psychiatrist 
of  large  experience  in  Germany  and  the  Orient,  also  informs  me  that — 

In  China  and  Japan  in  general  there  are  the  same  kinds  of  mental  diseases  as  in 
our  asylums  (of  German).  In  Japan  ...  I  saw,  for  instance,  many  cases  of  hebe- 
phrenia or  dementia  pra-cox,  imitating  the  voices  of  animals,  and  it  was  explained  to 
me  that  they  fancy  themselves  to  be  "bewitched"  into  beasts,  wolves,  dogs,  or  hens. 

In  connection  with  the  foregoing  we  must  remember  that  the  Egyptians 
represent  the  remains  of  one  of  the  oldest  civilizations,  in  a  state  of  regres- 
sion, while  Japan  is  an  example  of  an  also  ancient  civilization,  which  has 
taken  on  within  a  half-century  most  tremendous  evolutionary  stride. 

The  case  noted  in  a  Sudanese  negress,  by  Peterson,  near  the  otlier  point 
of  the  scale,  indicates  that  dementia  prsecox  is  not  necessarily  a  disease  of 
higher  civilization,  while  it  may  be  more  common  in  such. 

The  biologic  significance  of  the  foregoing  may  be  postulated,  for  our 
present  purpose,  as  follows : 

(1)  The  efficiency  in  the  "struggle  for  existence'^  of  races  and  nations 
will  be  adversely  affected  in  proportion  to  the  mentally  deficient  of  all  types, 

Page   2-.e 


F.  IV.  LANG  DON 


contained  in  their  populations.  Of  these  dementia  praecox  is  of  the  greatest 
importance  because  of  its  numerical  preponderance  and  of  its  incidence  at 
the  most  ambitious  and  productive  period  of  life,  when  the  foundations  are 
being-  laid  for  the  highest  achievements  of  the  race,  as  well  as  its  per- 
petuation. 

Hence,  the  chances  for  supremacy,  or  inferiority,  or  even  the  very  exist- 
ence of  a  nation  or  race,  may  hinge,  in  the  future,  upon  its  proportionate  pop- 
ulation of  subjects  of  dementia  prsecox. 

Turning  from  these  matters  of  racial  and  national  biologic  bearing  to 
those  of  individualistic  significance — what  evidence  have  we  which  may 
throw  light  on  the  fundamental  nature  of  dementia  praecox  ? 

Three  views  are  current  with  respect  to  the  underlying  processes  of  the 
disorder,  which  is  evidently  more  than  a  mere  psychosis. 

First :  That  it  is  due  to  some  unknown  toxin  or  toxins  of  specific  char- 
acter to  this  disease  and  producing  no  other.  Such  toxin  may  act  directly  on 
the  nervous  mechanism  through  the  nutrient  fluids  or  indirectly  by  disturb- 


Fig.  2.  Chimpanzee:  Hand  showing  non-rotation  of  terminal  phalanx  of  thumb. 
ilnring  flexion. 

(Photo,   by    Dr.    W.    H.    11.    Stod<lart.) 

ances  of  organs  of  internal  secretion.  In  the  latter  case  bv  ])roducing  a  sec- 
ondary "endocrinopathy." 

There  is  nothing  in  the  nature  of  the  disorder  inherently  opposed  to  the 
"specific  disease"  hypothesis,  which  is  held  by  eminent  investigators — among 
them  Kraepelin"  himself.  It  must  be  admitted,  however,  that,  until  recently, 
evidence  of  an  accepted  pathologic  nature  has  been  lacking  and  clinical 
observation  is  not  satisfying. 

The  recent  extremely  important  researches  of  Southard,'  however,  with 
his  findings  in  90  per  cent,  of  fifty  cases,  of  "evidence  of  general  or  focal 
brain  atrophy  or  aplasia,  when  examined  post-mortem,  even  without  the  use 
of  the  microscope" — throw  a  strong  light  on  this  aspect  of  the  disease. 
Southard's  investigations  and  conclusions  are  so  remarkable  for  wealth  of 
detail  as  well  as  conciseness  of  statement  that  no  abstract  could  do  justice 
to  them — and  the  reader  is  therefore  referred  to  the  original.  His  con- 
clusion is  that  dementia  praecox  must  be  removed  from  the  class  of  func- 
tional psychoses  and  placed  with  the  .<;tr)tctitral  diseases. 


RAXSOHOFF  MEMORIAL  VOLUME 


Secondly :  There  is  the  view  of  Stoddart,  Mott,  Adolf  Meyer,'  Hoch' 
and  others,  that  in  the  dementia  prjecox  patient,  we  are  dealing  with  an 
organism  inherently  defective  in  make  up.  or  of  incomplete  evolution  which 
is  unable  by  reason  of  such  incompleteness  to  effect  the  proper  "adjust- 
ments" to  the  increasingly  complex  conditions  of  existence,  incident  to 
puberty  and  adolescence.  Some  evidences  pointing  in  the  direction  of  this 
solution  of  the  problem  are  offered  on  subsequent  pages. 

The  third  view  rests  on  the  postulate  that  the  defective  adjustments, 
which  are  obviously  present,  are  due  to  psychogenic  causes,  chiefly  or  en- 
tirely. In  other  words,  the  organism  may  be  good  or  fair  inherently,  but 
its  "psychic  mechanism  has  been  accidentally  shunted"  on  to  a  wrong  track 
by  conditions  ("conflicts")  too  complex  for  its  resistance.     (Bleuler.'") 

C.  Macfie  Campbell"  has  contributed  a  comprehensive  and  illuminating 
survey  of  the  subject.  If  it  be  permissible  to  "summarize  his  summary" 
the  writer  would  do  so  as  follows : 

Many  authors  .  .  .  have  regarded  the  symptoms  as  merely  the  incoherent  expres- 
sion of  the  disordered  activity  (jf  pc^i^icned  nerve  tissue.  .  .  .  Meyer  (Adolf)  has 
formulated  a  conception  of  the  discrder  which  expresses  the  fact  that  the  psychosis  is 
the  culmination  of  a  long-continued  period  of  unhealthy  biological  adjustments  in  indi- 
viduals who  are  constitiitionolly  apt  tn  meet  their  difficulties  in  an  inadequate 


Fig.  3.  Chimpanzee;  Hand  showing  noii-rotatioii  of  terminal  phalanx  of  thumb. 
during  fle-xion. 

The  following  dictum  in  the  same  article  (by  Campbell)  contains,  to  the 
present  writer's  views,  the  gist  of  the  whole  question : 

Alienists  should  surely  be  the  first  to  recognize  that  human  biology,  if  it  is  to 
embrace  adequately  the  facts  of  experience,  must  be  psychological :  fysychology  is  not  a 
branch  of  philosoj'hy,  but  that  department  of  biology  z<.'hich  deals  zvith  the  most  com- 
plex reactions.     (Italics  by  present  writer.) 

For  the  sake  of  brevity  and  convenience  we  may  designate  the  three  views 
outlined  above  as:  The  "specific  disease,"  the  "subevolutional"  and  the 
"psychogenic"  hypotheses.  All  are  worthy  of  the  most  detailed  and  serious 
consideration,  but  the  title  of  the  present  paper  must  limit  its  scope  mainly 
to  consideration  of  the  two  latter  views. 

To  the  writer  the  second  and  third  postulates  seem  not  only  compatible 
with,  but  essential  to,  each  other.  Reduced  to  a  homely  simile,  the  one  says 
in  effect :  "The  wagon  breaks  because  it  is  too  -ojcakly  constructed  for  the 
load"  ;  the  other,  "The  wagon  breaks  because  the  load  lias  become  too  heavy." 

It  is  a  fundamental  principle  of  biology,  that  we  may  ne\er  comprehend 
an  organism  except  in  relation  to  its  antecedents  and  environment. 

Page  S78 


F.  IV.  LANGDOH 


Looking  at  the  dementia  prscox  problem  in  this  light,  what  evidence 
may  we  find  pointing  to  possible  structural  and  physiological  recessions  or 
atavisms,  as  accounting  for  the  mal-adjustments  which  characterize  its 
presence. 

The  human  hand,  in  the  evolutionary  procession  of  the  ages,  has  become 
much  more  than  the  mere  organ  of  locomotion  and  prehension  which  are 
its  primary  functions  in  the  lower  vertebrates.  By  reason  of  its  "adapta- 
bility," under  cerebral  influence,  it  has  become  a  highly  developed  instrument 
of  skill  and  jjrecision.  As  such,  it  has  needed,  and  acquired,  modification  of 
structure.  Such  modifications — of  "recent  acquirement" — biologically  speak- 
ing, are  the  first  to  be  lost  as  a  result  of  failures  in  adaptation  (adjustment 
in  general),  in  accordance  with  the  accepted  law  of  pathologic  degenera- 
tion, "last  to  develop,  first  to  decay."    It  has  gradually  added  to  its  primary 


Fig.  4.  Dementia  prscox  :  Showing  flat  thenar  eminence,  and  "/>(7(/"  of  thumb 
directed  forward. 

functions,  those  of  defence  and  ofifence,  of  the  hunter,  the  fisherman,  the 
artisan  and  the  artist ;  and  finally  in  the  higher  races,  it  has  developed  into 
an  "organ  of  expression"  second  only  in  importance  to  the  facial  and  ocular 
musculature. 

As  such  organ  of  expression  it  is  not  only  an  important  adjunct  to  spoken 
language  in  the  orator,  the  actor  and  the  "man  in  the  street,"  but  has  even 
replaced  spoken  language  successfully  in  the  deaf-mute,  and  more  or  less 
efficiently  in  communication  between  alien  peoples.  Its  importance  in  human 
affairs  is  recognized  in  such  current  expressions  as :  "The  Hand  of  God" ; 
"the  hand,  the  servant  of  the  brain" ;  the  "minister  of  reason  and  wisdom" 
(Cresollius).  We  speak  of  an  unusually  useful  person  as  "handy  to  have 
around."  It  is  not  strange,  therefore,  that  in  its  numerous  variations  and 
deficiencies  some  should  tend  to  be  atavistic  in  type,  or  indicative  of  incom- 
jileteness  in  an  evolutionary  sense. 

Comple.vity  of  function  implies  a  correspondingly  complex  development 
in  structure  in  any  organ ;  and  as  the  hand  is  readily  accessible  to  observa- 

Paoc  in:i 


RAXSOHOFP  MEMORIAL  VOLUME 


tion,  it  is  natural  that  the  attention  of  astute  clinicians  should  have  been 
attracted  to  its  pecularities  in  the  subjects  of  various  psychic  anomalies. 

In  civilized  life,  the  handshake  is  to  be  viewed  as  a  motor  expression  of 
emotional  feeling;  and  as  such,  of  varied  characteristics,  from  the  mere 
formal  "touch"  of  the  finger-tips  to  the  hearty  hand-grasp  of  the  warm  friend 
in  expressing  his  pleasure  at  meeting  you  after  a  long  absence. 

As  an  organ  of  emotional  language  it  is  natural  that  its  motor  "expres- 
sions" should  be  listless  and  defective  in  dementia  prsecox  subjects ;  and  we 
lind  that  this  is  the  case. 

Kraepelin/-  in  his  lectures,  repeatedly  calls  attention  to  the  peculiar 
mode  of  response  of  dementia  ]ir?ecox  patients  to  the  ordinary  salutation 
of  ottering  the  hand. 


'J"o  cjuote  from  his  clinical  lectures ; 

"...  I  may  call  your  attention  to  the  fact  that,  when  you  olTer  him  your  hand, 
the  patient  does  not  grasj'  it,  but  only  stretches  his  own  hand  out  stiffly  to  meet  it. 
Here  we  have  the  first  sign  of  a  disturbance  which  is  often  developed  in  dementia 
prwcox  in  a  most  astounding  way." 

Again,  in  his  8th  Edition,'-'  he  mentions  the  "hand-shake"  as  "cold, 
clammy,  lifeless,  heavy,  exerting  no  pressure." 

The  present  writer  in  demonstrating  these  peculiarities  in  his  clinics  has 
referred  to  this  "physical  sign"  as  "the  Kraepelinean  hand-shake."  It  evi- 
dently deserves  to  rank  as  a  physiological  stigma  of  importance. 

To  Stoddart,"  however,  is  due  the  great  credit  for  discovery  of  certain 
pecularities  of  a  structural  character  in  the  hands  of  dementia  prsecox  sub- 
jects, which  in  a  measure,  may  be  correlated  with  this  characteristic  hand- 
shake. 

To  this  type  of  hand  he  has  applied  the  designation  "Simian" — for  obvi- 
ous reasons.  For  some  of  the  illustrations  of  it  accompanying  this  paper  the 
writer  is  greatly  indebted  to  the  kind  courtesy  of  Dr.  Stoddart.  They  are 
reproductions  of  photographs  taken  by  himself.  This  type  of  hand  may  be 
described  as  follows: 


/■.  IV.  LANGDON 


THE  SIMIAN  TYPE  OF  HAND  OF  STODDART. 

(  1 )  With  the  hand  open,  the  fingers  and  thuml)  fully  extended  and  the 
inter-digital  spaces  closed — the  palmar  surface  of  tJie  thuuib  faces  forward 
— on  the  same  plane,  or  nearly  so,  as  the  palmar  surfaces  of  the  lingers.  ( In 
the  normal  hand,  the  palmar  aspect  of  the  Ihunib  faces  at  a  right  angle  to 
that  of  the  fingers  or  nearly  so.) 

(2)  When  the  thumb  is  flexed  its  teniiiiial  phalanx  does  not  rotate 
inward — or  does  so  in  a  less  degree  than  usual.  (In  the  normal  hand  it  does 
rotate  inward,  thus  contributing  to  greater  accuracy  and  power  of  a])position 
of  thumb  and  finger  tips.) 

(3)  The  fingers  are  markedly  hyper-exleiisible  at  the  metacarpo- 
phalancjeal  joint.     In  some  instances  they  may  be  "sent  backward"  to  a  right 


fPhoto.   I.y    n..    K.    A.   Xoilh.l 
Fig.  6.     Dementia  prifcox  ;     Shi)vviiii>  li\  pcr-cxtcnsililc  lingers  at   Metaearpo-plialan- 
Seal  joints. 

angle  with  the  metacarpus.  (  This  peculiarity  is  also  noted  in  many  grown 
imbeciles  and  in  young  children,  as  well  as  in  the  subjects  of  dementia 
prjecox.) 

Since  the  increasing  complexity  of  structure  and  function  of  the  hand 
in  man  is  determined  and  dominated  by  a  corresponding  com])lexity  of  the 
cortex  cerebri — it  is  not  difficult  to  correlate  a  deficiency  in  hand-structure 
and  function  with  lack  of  cortical  evolution. 

Stoddart'^  comments  on  these  manual  stigmata  as  follows: 

These  characteristics,  taken  in  conjunction  with  the  facts  that  they  are  sometimes 
encountered  in  cases  of  idiocy,  especially  those  of  the  Mongol  type,  that  imbeciles  are 
liable  to  develop  at  puberty  symptoms  resembling  those  of  dementia  praecox,  and  that 
the  above  peculiarities  of  the  hands  are  also  to  be  observed  in  the  chimpanzee,  all 
points  to  the  conclusion  that  dementia  praecox  should  be  regarded  as  a  failure  in  evolu- 
tion, as  an  atavism  or  reversion  to  an  ancestral  type. 

Nevertheless  we  are  bound  to  admit  that  atavism  does  not  entirely  account  for  all 
the  features  of  this  disease.  The  rapidity  of  the  deterioration,  the  physical  ill-health 
and  the  possibility  of  recovery,  though  rare,  all  indicate  that  some  active  morliid  process 
is  at  work. 

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RAXSOHOFF  MEMORIAL  rOLl'MF 


It  is  apparent  from  the  foregoing  that  Stoddart  inchnes  to  view  dementia 
l^rjecox  as  a  specific  disease  process  developing  upon  a  foundation  of  sub- 
evolution  or  atavism. 

Numerous  other  stigmata  of  degenerative  significance  are  present  in 
dementia  pr?ccox,  as  those  of  the  face,  jialate,  auricle,  etc.,  but  these  are 
common  to  the  subjects  of  various  psychoses — and  not  es])ecially  charac- 
teristic of  dementia  precox.  Hence  they  do  not  come  within  the  scope  of 
this  paper. 

A  review  of  the  literature  and  observation  of  the  diagnostic  methods 
of  many  psychiatrists,  has  led  the  present  writer  to  conclude  that  these  "hand 
stigmata"  are  overlooked  by  a  great  majority  of  clinicians — or  not  given  due 
weight  as  diagnostic  and  prognostic  indicators. 

His  personal  experience  has  convinced  him  of  their  decided  value  as 
factors  in  diagnosis,  especially  in  that  "doubtful"  class  of  cases,  sometimes 
labelled  "undifferentiated" — with  a  prefix  of  "depression,"  "elation,"  , 'hallu- 
cinosis," etc.,  as  the  case  may  be. 

They  are  also  often  of  value  as  guides,  in  very  early  stages  of  dementia 
prsecox ;  and  due  consideration  of  them  may  make  us  more  guarded  in  our 
prognosis  in  the  presence  of  apparently  "mild,"  "psychic  departures." 

Some  indication  of  the  frequency  of  occurrence  of  the  "Simian  type"  of 
hand  in  dementia  praecox  may  be  of  interest  in  this  connection.  My  asso- 
ciate, Dr.  Emerson  A.  North,  has  kindly  investigated  fijr  me  a  total  of 
forty-four  cases,  taken  consecutively,  without  selection,  in  two  institutions 
in  Ohio.     His  results  follow: 

Simian   stigmata:     Typical    (-|--|--f) 21 

Partial    {++) 14 

-Absent    8 

*Dou1)tful    1 

44 
The  cases  classed  as  "typical"  present  the  three  chief  "stigmata"  well 
developed ;  namely :    Thumb  facing  forward  ;  absence  of  internal  rotation  of 
its  terminal  phalanx ;  hyper-extensile  fingers  at  metacarpophalangeal  joint. 
Those  classed  as  "partial"  presented  only  two  of  the  "stigmata." 
In  thirty-five  cases  of  forty-four,  practically  80  per  cent.,  the  stigmata 
were  such  as  to  be  of  clear  diagnostic  value. 

By  way  of  contrast  we  may  note  that  the  "Simian  hand"  is  rarely  seen  in 
typical  manic-depressives.  The  writer  has  seen  a  number  of  patients  with 
"Simian"  hands,  diagnosed  as  manic-depressives  by  experienced  alienists 
and  has  so  diagnosed  some  others  himself — on  the  basis  of  mental  symp- 
toms; but  subsequent  observation  of  these  patients  has  shown  the  original 
diagnosis  to  be  erroneous,  and  the  course  of  the  disease  that  of  dementia 
prcvcox. 

In  addition  to  the  "hand-shake"  of  Kraepelin,  already  mentioned,  the 
"snout  cramp"  of  Kahlbaum,  noted  by  Kraepelin,  the  "shut-in  personality" 

♦Observations  not  truswortli.v  by  reason  of  extensive  deformity  o:  hands  by 
cicatrices  of  old  burns. 

Page  SS2 


F.  IV.  LANGDON 


of  Hoch,  the  "special  make-up"  of  Adolf  Meyer,  and  other  physiological 
observations,  might  come  up  for  consideration  as  of  biologic  significance,  but 
they  are  already  so  widely  known  and  discussed  that  a  mere  reference  to 
them  is  sufficient. 

Recently,  however,  mention  has  been  made  of  a  "sign"  of  possible  biologic 
bearing,  by  Steen,'-'  which  consists  in  a  characteristic  sitting  attitude, 
noted  by  him  as  "frequent"  in  dementia  ])raecox  subjects  and  described  as 
follows; 

The  arms  are  held  close  to  the  trunk,  with,  as  a  rule,  the  elbow  joint  in  a  condition 
of  stiff  extension;  the  hands  pronated  and  resting  on  the  lower  part  of  the  thighs,  or 
even  on  the  knees.  .  .  .  This  attitude  is  possibly  an  example  of  reversion,  and  is 
seen  in  the  statues  of  ancient  Egypt. 

He  therefore  calls  it  the  "Ancient  Egyptian  attitude." 

Finally,  as  we  go  about  our  daily  duties,  we  all  recognize  the  dementia 
praecox  "make-up"  as  a  practical  clinical  entity,  which  fact  of  itself  is  sug- 
gestive of  a  basis  of  biologic  significance. 

The  view,  based  on  results  of  the  Abderhalden  dialysis  method,  that  the 
disease  is  an  "endocrinopathy"  depends  on  evidences  of  various  morljid  pro- 
teins in  the  content  of  the  blood  serum. 

The  view  of  Orton"'  on  this  subject  may  be  here  ]M-esented  as  that  of  a 

competent  critic — 

F.ven  if  we  accept  the  theory  and  the  results  of  its  most  hopeful  investigators,  we 
are  only  brought  to  the  beginning  of  a  wide  field  of  investigation ;  as  by  the  interpre- 
tation of  the  theory,  the  results  speak  only  for  a  faulty  metabolism  in  specific  organs 
and  as  yet  give  no  light  on  the  underlying  causes,  i.  e.,  the  fact  that  the  metabolism 
of  the  testicle  and  brain  are  disturbed  gives  no  insight  into  the  cause  of  such  disturb- 
ance. 

To  the  present  writer  it  would  seem  quite  conceivable  that  the  indica- 
tions of  wide-spread  defects  in  various  organs  and  their  premature  degen- 
eration— even  if  established,  are  also  logically  attributable  to  general  defi- 
ciencies of  "make-up"  and  consequent  undue  susceptibility  to  infectious  or 
other  disease  agencies.  In  other  words,  they  may  argue  in  favor  of  a  bio- 
logic or  basic  defect. 

To  sum  up : 

(1)  In  the  interpretation  of  the  role  of  the  biologic  factors  in  this 
psychosis,  so  far  as  the  evidence  available  at  present  permits,  we  must  recog- 
nize the  fact  that,  in  the  subject  of  dementia  prsecox,  we  have  to  deal  with 
one  of  the  "by-products"  of  the  "Laboratory  of  Nature,"  an  organism  inade- 
quate to  adjust  itself  to  its  normal  environment,  owing  to  an  arrest  of  evolu- 
tion and  a  premature  and  irregular  involution.  Such  an  organism  may  be 
likened  to  a  "proper  soil."  Not  every  yoittli  therefore  can  develop  a  dementia 
prcccox  form  of  break-down  of  the  psychic  mechanism. 

(2)  The  clinical  course  of  the  disease,  and  the  findings  of  Southard.' 
suggest  destructive  agencies,  which  may  influence  the  rate  and  amount  of 
"deterioration."  Here  the  "specific  disease"  element  must  be  considered  as 
a  possibility.    Such  element  may  be  viewed  as  playing  the  role  of  a  noxious 

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RAXSOHOFF  MEMORIAL  VOLUME 


weed,  or  destructive  parasite,  damaging;  the  immature  mental  "crop"  already 
started. 

f3)  Psycliogeiiic  factors  (situations,  conflicts,  etc.)  may  quite  plausibly 
he  likened  to  "the  seed."  determining  the  character  of  the  subsequent  "abnor- 
mal crop."  /.  c,  the  "form  and  content"  of  the  psychosis,  its  "trends"  and 
other  psychic  activities. 

CONXLUSIOXS. 

The  mere  presentation  of  evidence  of  the  nature  of  a  disease  is  obviously 
of  litlle  practical  value  in  itself.  To  be  fruitful  in  results  it  should  point 
the  way  to  constructive  lines  of  thought.  What  useful  lesson  may  we  learn 
from  a  study  of  these  various  biologic  asf^ects  of  dementia  pnecox? 

Since  "mind"  in  its  complete  expression,  includes  the  end  results  of  all 
reactions  of  the  animal  organism  to  its  environment,  it  is  obviously  impos- 
sibl»^  to  draw  a  sharp  scientific  line  of  demarkation  between  psychology  and 
psychiatry.  The  phenomena  of  the  two  sciences  may  be  said  to  represent 
merely  difTering  results  of  "rustling  of  the  leaves"  on  the  higher  branches 
of  the  "tree  of  biology."  Our  distinctions  therefore  are  often  arbitrary, 
based  on  the  expediency  of  social  conduct.  Hence  they  may  vary  in  different 
races  and  in  the  same  race  at  different  stages  of  development.  The  same 
truth  applies  to  individuals. 

Any  practical  plan  of  theraiiy  for  dementia  pra?cox  should  recognize  the 
biologic  tripod  of  sith-evolution.  ncuro-toxccmia.  and  faulty  psycho-genesis 
as  the  probable  basis  of  the  disease.  Our  efforts  therefore  should  be  directed 
toward  improving  the  "soil."  remo\al  of  "weeds"  and  changing  the  "crop." 
The  obvious  indications  are.  (a)  removal  of  the  patient  from  sources  of 
"psychic-conflicts"  and  "difficult  adjustments"  at  as  early  a  stage  as  possible. 
This  means,  of  course,  in  practically  every  case,  removal  from  home  and 
home  influences;  (b)  rest,  physical  and  mental.  /;i  bed.  during  the  acute 
stage,  so  that  the  physiological  energies  may  be  conserved  and  resistance  to 
the  toxic  element  may  be  promoted;  (c)  attention  to  anemia  and  other  mor- 
bid blood  states — if  a  leucocytosis  could  be  induced  it  would  probably  be 
desirable  in  some  cases;  (d)  eliminative  measures  by  hydrotherapy  and 
otherwise  are  very  important;  (e)  nutritional  and  constructive  agencies 
must  be  pushed  to  the  limit. 

As  general  health  and  well-being  improve  under  this  course,  moderate 
exercise  in  the  open  air  and  suitalile  occupational  and  diversioiial  therapy 
become  useful. 

The  difficulties  of  productive  psycho-analysis  and  psycho-therapy  are 
obviously  great,  in  the  fully  developed  psychosis,  but  their  possibilities  in 
very  early  stages  of  the  disease  may  be  correspondingly  great. 

Under  the  above  outlined  methods  of  management,  some  cases  improve 
so  as  to  be  able  to  resume  family  and  social  life  to  some  extent;  others  rank 
in  statistics  as  "recovered,"  though  it  is  probable  that  they  would  be  more 
correctly  labelled  "recovery  rvith  defect."  It  is  conceivable,  however,  that 
in  exceptionally  favorable  subjects,  in  an  early  stage  of  the  illness,  under  the 

Page  2&k 


F.  IV.  LANGDON 


modes  of  management  just  outlined,  tlie  neuro-toxic  element  of  the  disease 
may  "run  its  course,"  leaving  a  minimum  of  deterioration  :  and  that  (he 
dynamic  impulses  of  a  beneficent  nature,  latent  for  a  time,  now  relieved  of 
their  handicap,  may  reassert  their  powers.  Evolution  may  then  go  on  to  a 
fairly  normal  completion  — for  that  individual.  These  are  the  cases  that  may 
he  said  to  really  "reco\cr."  They  are  rare,  hut  they  encourage  us  to  try  and 
to  hope. 


KEFERENCES. 

1 

Kinf.    Captain    Kdgar. 

M.    C.    V.    S.    A 

,.  :       Mental     Disease    a 

ml     Defect    in     fnil 

cl     Stat 

Troops.' 

War  Dept.,  Office  of  T 

he    Surgeon    Cenei 

-al.   Bulletin   No.  5.   M 

arch.    19M. 

N.   Y.  Times:      Kditori 

al.    May    17.    1916. 

3. 

Peterson,    Frederick,    N 

.    v.:      Personal    , 

lommunication    Februa 

ry    4.    1916. 

4. 

Ibid.:     Febrnary   12,   1916. 

5. 

Lilienstein,   S..  Bad  N: 

luheim.  Germany: 

Personal   communica 

tion,  March  6,    19li 

6. 

Kraepelin:      Psychiatric 

e.    1913. 

7. 

Southard,   K.   E.:     On 

the  Topographical   Distribution  of  Cortc 

;x   Lesions  and   .Am 

jmalies 

iu 

Dementi 

ia  Pncco.x.  with  Some  Ac 

count  oi  their  Fui 

ictional  Significance. 

Amcr.  Jour.  Insanil 

:y,    LXX 

383,   603,  October,    191-)-Jani,ary, 

1915. 

8. 

Meyer,    Adolf:      The    I 

)vnamic    Interpret 

ation    of    Dementia    Pi 

•iccox.      Amer.    Jour 

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chology. 

XXI,  July,    1910,   385-403. 

9. 

lloch,    August:      Const 

;itutional    Factors 

in    the    Dementia    Pr: 

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.\cur. 

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Psych., 

Vni,  August,  1910,  -163. 

10. 

Ouoted  bv  Hoch:     Rei 

new   of  Bleukr's 

Schizophrenia.      Rev. 

of    Neur.    &    Psych.. 

X.    Jun 

e. 

1912,    259" 

11. 

Campbell,    C.    Macfie: 

A    .Modern    Con 

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Pr.ecox.       Rev.    of 

Xenr. 

& 

I'-sych.. 

Vll,  October,   1909,  623. 

IT 

Kvaenelin.    Emil:      I.ec 

Uirt-s    on    Clinical 

Psychiatry.       English 

tra.i-lation    by    T,    ; 

c. 

N.   V.,"\Vm.   Wood  &  Co..   190-4.  . 

U. 

Kraepelin.    K.:      I'syrln 

.It,  if,    ,Stl,    c.l,    19 

13. 

u 

Stn,l,l.-,rt.    W.    II.    1!.: 

-Mi,„l    and    Us    1) 

isorders.    London.    1908,    230,    231.       Same 

2nd    e. 

1.. 

.UX-.l.Vi. 

1  ; 

SI.,,,,     K,     11    :       .\    CM; 

lr:,ctcristic    Attitu, 

lie,    etc.      .Tour.    Ment. 

Sci.,    Januaiy,    191 

6,    p.     17 

9. 

(Ollot,  , 

1    1 ,    l;,v     N\l,r.    &    P-y 

vh..    .March,    1916, 

p.   132.) 

1... 

1  ),!,,,,,     S,,,ni,i-I     -I',;       -1 

n.,-    l',.-eut    Stat, 

..s    of    the    .\ppl,cali,.n 

..f    the    AberhaUIei 

,    Dialy. 

■  is 

.\letliod 

to    ]■•.         ■  ,!:■■            ^11,-   , 

In 

a(|,l,ii.  ,     :..    1    ■     ■  •,.  ■ 

.i.ful   acknowlcdg 

ments   a 

re 

due  to 

my   1, :-     .■    1  '       w 

.     1  .  rinan;   to  my 

Ors.  Ji. 

A.    \\,ll,,:,„.   ,:,■,!    I-,,,,,. 

'-.,.'    \     .\.>,ili    ,,,, 

,  ;i)i,.  ,ii    .1,1.1    .I..II   I.,  .i: 

.l..ta   and   some  of 

the  ilU 

is- 

trations 

;   to   i>r,    !■.    U.    H.irmon. 

1.-    ll..spilai,    Ciiicnnaii 

.   tor  the  courtesies 

of  acce 

to   the   ' 

wealth   of   material  conla 

lution,    and    to    Dr.    11 

.    Douglas    Singer    f 

or    valu. 

ed 

suggestions  and 


PERNICIOUS  ANEMIA  WITH  MENTAL  SYMPTOMS 

OBSF.RVATIONS  ON  THE  VARYING  EXTENT  AND  PROBABLE  nURATIOX' 

OF    CENTRAL    NERVOUS    SYSTEM    LESIONS    IN 

FOUR  NECROPSIED  CASES.* 

Loi'is  A.  Li'iuK.  M.A.,  M.D. 

Cincinnati 

r)iir  l<no\vledg;c  of  pernicious  anemia  is  Iteing  constantly  enriched,  espe- 
cially our  knowledge  relating  to  the  changes  occurring  in  the  nervous  system. 
And  justly  .so,  because  after  all,  next  to  the  blood  changes,  the  most  char- 
acteristic and  frequent  clinical  findings  are  on  the  part  of  the  central  nervous 
system.  Minnicht  (1893)  demonstrated  lesions  in  the  spinal  cord  in  approx- 
imately 70  per  cent,  of  cases  of  pernicious  anemia.  Of  forty-one  ca.ses 
treated  by  Billings  (1900),  forty  showed  neurological  symptoms.  In  a 
very  recent  (1919)  report  of  the  150  moderately  advanced  cases  of  per- 
nicious anemia  examined  at  the  Mayo  Clinic,  W'oltman  found  indisputable 
evidence  of  nervous  tissue  disintegration  in  over  80  per  cent. 

Formerly  the  neuropathology  of  this  disease  consisted  chiefly  in  descrip- 
tions of  the  changes  taking  place  in  the  spinal  cord.  It  has  been  but  com- 
paratively recently  that  investigation  has  shown  that  these  changes  are  not 
limited  to  the  cord,  but  involve  other  parts  of  the  central  nervous  system 
••IS  well.     (Pfeiffer.  P.arrett,  Woltman.) 

ETIOLOGIC   FACTORS. 

In  discussing  the  etiologic  relationship  between  the  brain  and  cord 
changes  on  the  one  hand  and  the  blood  changes  on  the  other,  one  is  con- 
fronted by  various  theories,  each  of  which  has  its  ardent  supporters.  The 
reason  for  this  diversity  of  opinion  is  our  ignorance  of  the  fundamental 
cause  or  causes  underlying  this  disease.  Practically  all  are  agreed  that  the 
clinical  .syndrome  which  we  call  pernicious  anemia  is  produced  by  one  toxin, 
the  nature  and  origin  of  which,  however,  are  still  mooted  points. 

We  feel  safe  in  assuming  that  the  disease  is  due  to  a  toxin  because  of 
experimental  work  performed  along  similar  lines  in  cases  of  anemia  due  to 
the  Bothriocephabis  latus.  It  was  long  known  that  all  individuals  harbor- 
ing these  parasites  did  not  develop  pernicious  anemia.  Of  those  that  did 
develop  it  nothing  was  disclosed  either  during  life  or  at  necropsy  to  show 
that  they  possessed  any  characteristics  that  might  be  regarded  as  predis- 
posing them  to  this  disease.  The  natural  inference,  then,  was  that  the  para- 
site was  the  variable  factor.  In  other  words,  some  change  Dccinrcd  whicii 
transformed  the  parasite  from  a  harmless,  though  unwelcome,  inhabitant  of 
the  intestinal  tract  into  a  dcadlv  menace. 


LOUIS  A.  LURIE 


Elaborating  on  this  idea,  Shapiro  advanced  the  theory  that  when  the 
worm  died  or  became  diseased,  noxious  substances  were  produced  which  on 
being  absorbed  produced  the  anemia.  The  work  of  WiUschur  strongly  sup- 
ports this  view^  He  examined  twelve  worms,  the  removal  of  which  cured 
severe  anemias  and  found  that  in  "all  cases  the  worms  were  either  dead, 
decomposed,  or  sick." 

Reasoning  by  analogy,  we  feel  confident  that  the  Addison-Biermcr  ty]5e 
of  anemia  is  also  due  to  a  toxin.  As  to  its  origin,  we  as  yet  know  nothing 
very  definite.  Much  work  has  been  done  in  this  connection.  The  regularity 
with  which  changes  occur  in  the  gastro-intestinal  tract,  has  led  many  to  be- 
lieve that  this  condition  is  essentially  a  disease  of  the  gastro-intestinal  tract 
(Grawitz-W.  Hunter).  Atrophy  of  the  gastric  mucosa,  achylia  gastrica,  and 
intestinal  stasis  are  frequently  encountered.  Berger  and  Tsuchiya  found  that 
extracts  of  the  gastric  and  intestinal  mucous  membrances  from  patients  dead 
of  this  anemia  were  more  hemolytic  than  extracts  of  normal  mucous  mem- 
branes.   This  statement,  however,  is  disputed  by  Ewald  and  Freidberger. 

It  is  well  known  that  certain  chemical  substances,  such  as  oleic  acid, 
saponin,  phenylhydrazin,  b-amino-azolyl-ethylbenzaldehyd  and  p-oxypheny- 
lethylamin  are  capable  of  producing  intense  hemolysis.  One  of  these  sub- 
stances, namely  p-oxyphenylethylamin,  has  been  isolated  by  Iwao  from  auto- 
lyzing  pancreas,  putrefying  horse  flesh  and  from  Swiss  cheese.  Conceivably 
this  compound  may  arise  in  the  intestinal  tract  as  the  result  of  decomposition 
of  food.  Berthelot  and  Bertrand  have  shown  that  among  the  flora  of  the 
intestinal  tract  there  is  a  bacillus,  the  B.  aminophilus — which  is  capable  of 
jiroducing  p-oxyphenylethylamin  from  tyrosin.  Thus  we  can  readily  see 
how  intestinal  stasis  could  be  a  great  factor  in  the  production  of  pernicious 
anemia. 

On  the  other  hand,  others  have  taken  the  stand  that  the  increased  pro- 
duction of  hemolysins  is  due  to  a  condition  of  hypersplenism.  The  toxin  is 
carried  by  the  blood  to  the  spleen  where  certain  changes  occur.  According 
to  Moftit,  "erythrolysis  does  not  take  place  in  the  spleen  but  in  some  way 
the  erythrocytes  are  sensitized  and  prepared  for  later  destruction  in  the 
liver,  marrow  or  lymph  glands."  From  this  viewpoint  it  would  be  easy  to 
account  for  the  beneficial  results  that  often  follow  splenectomy. 

Granting  that  a  toxin  is  responsible  for  this  condition  the  lack  of  the 
fundamental  knowledge  as  to  its  origin  and  modus  operandi,  makes  it  all 
the  more  difficult  in  trying  to  solve  the  causal  relationship  between  the  blood 
and  the  central  nervous  system  changes.  We  have  a  mass  of  clinical  and 
histopathologic  data  that  has  been  accumulating  ever  since  Addison  first 
described  pernicious  anemia  in  1855.  Investigators  have  naturally  tried  to 
correlate  these  facts,  and  in  correlating  them,  have  advanced  many  theories. 
Most  of  these  theories  have  long  since  fallen  by  the  wayside ;  others,  how- 
ever, have  remained  and  can  be  briefly  summarized  as  follows : 

1.  A  toxin  produces  the  anemia  which  in  turn  ]iroduces  another  toxin 
tliat  causes  the  changes  in  the  brain  and  spinal  cord. 

Page  mi 


RAXSOIfOFF  MEMORIAL  VOLUME 


2.  The  anemia  itself  acts  as  a  toxin  whicli  tbrougli  malnutrition  causes 
the  changes  observed  in  the  central  nervous  system. 

3.  The  toxin  acts  independently  on  the  blood  and  on  the  central  nervous 
system. 

Before  discussing  the  relative  merits  of  tlicse  theories  it  is  essential  to 
bear  in  mind  certain  well  established  facts.  The  absolute  lack  of  corre- 
spondence between  the  brain  and  cord  changes  on  the  one  hand  and  the 
anemia  on  the  other  hand  both  from  anatomic  and  clinical  standpoints  has 
long  been  known. 

Clinically  there  are  many  cases  in  which  the  neurological  symptoms  ap- 
]iear  before  the  anemia.  In  other  cases,  both  conditions  arise  simultaneously, 
and  in  still  other  cases,  the  anemia  is  present  long  before  the  appearance  of 
any  neurological  disturbances. 

Similarly,  either  condition  may  improve  without  a  corresponding  im- 
provement in  the  other,  or  both  may  show  a  co-ordinate  improvement. 

Furthermore,  it  has  been  stated  (Goebel)  that  cases  that  clinically  show 
disturbances  of  the  central  nervous  system  may  on  section  show  no  demon- 
stral)le  organic  changes. 

From  the  above  statements,  it  is  obvious  that  the  first  two  theories  are 
untenable.  So  long  as  it  is  possible  for  the  nervous  symptoms  to  precede 
the  appearance  of  the  anemia,  then  it  is  impossible  to  maintain  that  the 
anemia  either  directly  or  indirectly,  that  is,  through  the  production  of  an- 
other toxin,  produces  the  cord  and  brain  changes. 

The  third  theory,  however,  overcomes  this  objection.  If  we  assume  that 
the  toxin  acts  independently  on  the  central  nervous  system  and  on  the  blood, 
then  we  can  say  that  in  one  instance,  the  toxin  acts  first  on  the  central  nerv- 
ous system  and  then  on  the  blood,  thus  producing  those  cases  in  which  the 
disease  is  ushered  in  by  the  nervous  .symptoms.  In  another  instance,  it 
acts  on  the  blood  first.  These  are  the  cases  in  which  the  anemia  precedes 
the  development  of  neurological  symptoms.  In  still  another  instance,  the 
toxin  acts  simultaneously  on  the  central  nervous  system  and  on  the  blood, 
thereby  giving  rise  to  a  clinical  picture  showing  both  brain  and  lilood  changes 
at  once.     (Nonne-Billings.) 

So  far  so  good.  But,  on  the  basis  of  this  theory,  how  can  we  explain 
the  fact  that  in  cases  where  similar  therapeutic  measures,  for  example, 
splenectomy,  have  been  instituted,  some  will  show  an  improvement  in  the 
neurological  symptoms  without  any  improvement  in  the  blood  picture,  while 
others,  reversely,  will  show  a  betterment  in  the  anemia  without  a  correspond- 
ing betterment  in  the  cord  and  brain  changes. 

^  Decastello^  performed  a  splenectomy  on  a  patient  who  had  sutYered  from 
the  disease  for  less  than  a  year.  The  anemia  was  severe  and  the  spleen 
but  slightly  enlarged.  Since  the  operation,  the  patient  has  shown  marked 
improvement  clinically  but  with  no  alteration  in  the  blood  picture. 

liarpole.'  on  the  other  hand,  i^erformed  a  splenectomv  on  a  i^alient  who 


LOUIS  A.  LURIE 


had  been  known  to  have  had  the  disease  for  at  least  two  years.  The  anemia 
was  moderatelv  severe.  Followin_e;  the  operation  there  was  an  immediate 
improvement.  The  patient  has  continued  in  fair  heaUh  with  only  a  sHght 
anemia  but  with  persistence  of  the  spinal  cord  svinptonis. 

Furthermore,  how  will  this  theory  account  for  those  cases  which  showed 
clinical  evidence  of  involvement  of  the  central  nervous  system,  but  in  which 
the  pathologist,  on  necropsy,  is  unable  to  discover  any  demonstrable  lesion? 

It  seems  to  me  that  if  we  judiciously  combine  the  second  and  third 
theories  into  some  such  theory  as  the  following,  we  shall  have  one  that  will 
account  for  all  of  the  various  manifestations  of  pernicious  anemia.  Briefly 
stated  it  would  read  as  follows ; 

1.  One  toxin  produces  pernicious  anemia. 

2.  This  toxin  acts  independently  on  the  blond  and  on  the  central  nervous 
system. 

3.  The  anemia  itself,  after  it  has  persisted  for  a  considerable  length  of 
time,  interferes  with  the  metabolism  of  the  nerve  cells,  thereby  indirectly 
enhancing  the  poisonous  action  of  the  toxin  so  that  instead  of  being  merely 
an  irritant  to  the  nervous  tissue,  it  becomes  a  highly  destructive  agent.  In 
this  way,  the  changes  which  at  first  were  purely  temporary  and  functional 
now  become  permanent  and  organic. 

In  other  words,  I  think  that  we  can  with  justice  assume  that  the  nervous 
structure  is  open  to  two  lines  of  attack,  namely,  (  1  )  a  direct  or  frontal  attack 
by  the  toxin,  and  (2)  an  indirect  or  flank  attack  liy  the  anemia.  If  the 
anemia  is  improved  before  the  latter  attack  has  materalized  we  get  an  im- 
provement in  the  neurological  symptoms  and  such  a  patient  on  necropsy  will 
show  no  pathologic  cord  or  brain  lesions. 

If,  however,  the  anemia  has  persisted  long  enough  for  both  froirtal  and 
flank  attacks  to  materialize,  then  improvement  in  the  blood  picture  will  not 
be  followed  by  a  corresponding  improvement  on  the  part  of  the  central 
nervous  system.  Such  cases  coming  to  necropsy  will  show  the  changes  that 
are  usually  found  in  the  cords  and  brains  of  pernicious  anemia  patients. 

This  theory  is  in  line  with  the  views  of  Bonhoefifer,  who  thinks  that  the 
psychoses  that  some  patients  present  are  not  due  to  the  direct  action  of  the 
toxin  but  to  the  interposition  of  some  metabolic  changes  in  the  nerve  cells. 

Christian's  recent  work  strengthens  this  view  also.  He  tested  the  renal 
function  in  fourteen  cases  of  pernicious  anemia  and  found  that  the  latter 
produced  a  chronic  nephritis  which  could  be  improved  by  improvement  of 
the  anemia,  provided  the  latter  had  not  persisted  for  too  great  a  length  of 
time.    His  conclusions  are  : 

In  patients  with  pernicious  anemia  the  disease  is  accompanied  by  a  disturl)ance  of 
renal  function,  as  measured  t:)y  renal  dietary  tests,  which  is  similar  to  that  found  in 
patients  with  advanced  chronic  nephritis.  In  these  patients  there  is  no  other  evidence 
of  chronic  nephritis  and  the  disturbance  appears  to  be  due  to  the  anemia,  decreasing 
with  the  subsidence  of  the  severity  of  the  anemia  unless  the  anemia  is  maintained  so 
long  that  a  permanent  disturbance  of  renal  function  ensues.     [Italics  mine.] 

Pa,/c  ,.'.s;i 


RAXSOHOFF  MEMORIAL  VOLUME 


Tliis  theory  stated  in  its  entirety  would  read  as  follows : 

1.  One  toxin  causes  both  the  blood  and  the  central  nervous  system 
changes. 

2.  This  toxin  acts  independently  on  the  blood  and  on  the  central  nervous 
system.  This  would  account  for  those  cases  in  which  (a)  the  neurological 
symptoms  manifest  themselves  before  the  anemia,  or  (b)  in  which  the 
anemia  precedes  the  brain  and  cord  changes,  or  (c)  in  which  both  condi- 
tions arise  simultaneously. 

3.  As  soon  as  the  typical  blood  picture  of  pernicious  anemia  develops 
and  persists  for  a  considerable  length  of  time,  the  metabolism  of  the  nerve 
cells  is  so  impaired  that  the  changes  which  were  purely  functional  at  first 
and  due  to  the  irritating  action  of  the  toxin  alone,  now  become  organic  and 
permanent.  Hence,  no  matter  how  greatly  the  physical  state  is  improved, 
be  it  through  splenectomy,  transfusions,  or  drugs,  no  improvement  on  the 
part  of  the  nervous  system  follows.  The  damage  is  irreparable.  If,  how- 
ever, the  hemolysis  has  not  lasted  very  long,  then  improvement  in  the  neuro- 
logical symptoms  may  be  expected  to  follow  the  exhibition  of  proper  thera- 
peutic measures.  We  can  thus  account  for  the  apparent  contradictory  results 
in  the  cases  reported  by  Decastello  and  Harpole.  In  the  latter  case,  the 
anemia  had  lasted  for  at  least  two  years.  Removal  of  the  spleen  was 
followed  by  an  improvement  in  the  blood  picture  but  with  no  improvement 
on  the  part  of  the  central  nervous  system.  Here  we  can  rightly,  assume  that 
the  anemia  had  interfered  to  such  an  extent  with  the  metabolism  of  the 
nervous  elements  that  permanent  lesions  had  been  produced. 

In  the  former  case,  the  anemia  had  existed  for  a  much  shorter  period 
and  therefore  splenectomy  was  followed  by  improvement  in  the  neurological 
symptoms. 

In  line  with  this  theory  is  the  fact  brought  out  by  Pearce,  Krumbhaar 
and  Frazier  and  their  co-workers,  that  if  splenectomy  is  performed  before 
the  blood  has  reached  an  extreme  degree  of  deterioration,  not  only  is  the 
operative  risk  lessened  but  the  improvement  is  greater  and  more  lasting. 

Finally,  on  the  basis  of  this  theory  it  is  easy  to  account  for  those  cases 
which  during  life  show-ed  clinical  evidence  of  involvement  of  the  central 
nervous  system  but  which  on  necropsy  showed  no  lesion,  either  in  the  cord 
or  brain.  In  these  cases,  (he  irritant  action  of  the  toxin  had  not  been  aided 
by  the  anemia. 

MENTAL  SYMPTOMS  OF  PERNICIOUS  .ANEMIA. 
Many  observers  have  called  attention  to  the  mental  symptoms  that  fre- 
quently occur  in  pernicious  anemia  patients.  The  early  investigators  simply 
noted  the  somnolence,  apathy,  and  coma  that  usually  preceded  the  fatal 
termination  of  the  disease.  Later,  however,  it  was  noted  that  the  mental 
symptoms  were  not  simply  terminal  but  that  in  a  great  many  cases  they 
constituted  a  dominant  part  in  the  clinical  picture.  Marcus  and  Langdon 
have  each  reported  cases  in  which  the  mental  changes  appeared  before  the 
Page  j;io 


LOUIS  A.  LURIE 


anemia  or,  at  least,  before  the  blood  picture  was  sufficiently  developed  to 
warrant  the  diagnosis  of  pernicious  anemia.  Langdon  termed  these  cases 
"prepernicious  anemia."  The  psychic  disturbances  may  range  from  mild 
depression  to  violent  maniacal  outbursts.  Some  cases  will  show  irritability, 
hyperkinesis,  delusions  and  hallucinations.  Other  cases  will  show  indiffer- 
ence, apathy,  and  severe  melancholia.  Whenever  a  distinct  psychosis,  such 
as  manic-depressive  insanity,  is  present,  the  majority  of  observers  look  on  it 
as  separate  and  distinct  from  the  pernicious  anemia.  At  most,  in  such  cases 
the  pernicious  anemia  may  be  regarded  as  a  predisposing  factor.  At  present 
it  is  generally  accepted  that  the  psychotic  manifestations  should  be  classified 
with  the  exhaustion  and  toxic-infectious  psychoses.  Barrett  expressed  it 
very  clearly  when  he  said: 

As  to  the  clinical  position,  it  would  seem  that  they  must  be  placed  anions  the 
paranoid  conditions  which  are  symptomatic  of  a  toxic  organic  process  affecting  the 
centra!  nervous  system — analogous  to  the  paranoid  conditions  which  have  been  noted 
in  tabes,  alcoholism  and  from  certain  drugs. 

It  has  been  but  comparatively  recently,  however,  that  efforts  have  been 
made  to  link  up  the  mental  disturbances  with  the  cortical  changes.  Barrett 
found  many  pathologic  changes  in  the  cortex,  but  as  a  whole  not  of  the  spe- 
cific type.  They  appeared  to  be  rather  similar  to  those  changes  which  occur 
in  conditions  of  chronic  intoxication,  due,  for  example,  to  chronic  alcohol- 
ism. The  blood  vessels  showed  the  most  constant  changes.  There  were  in 
the  nature  of  swelling  of  the  intimal  cells  and  in  some  active  proliferative 
changes.  The  most  important  findings,  however,  are  the  focal  lesions,  which 
correspond  very  closely  to  the  lesions  so  characteristically  present  in  tlie 
cord. 

W'oltman  made  a  very  thorough  and  exhaustive  study  of  seven  cases. 
His  findings  led  him  to  the  conclusion  that  the  brain  and  cord  changes  run 
fairly  parallel  and  with  about  the  same  frequency;  and,  furthermore,  that 
patients  who  show  degenerative  changes  in  the  spinal  cord  at  necrop.sy, 
usually  show  the  same  type  of  lesion  in  the  brain  also.  In  the  medullary 
substance  of  sections  of  different  levels  of  the  brain,  he  also  found  areas  of 
degeneration  of  the  Lichtheim  type  that  are  identical  with  those  that  are 
usually  found  in  the  posterior  and  lateral  columns  of  the  spinal  cord.  In 
addition  to  these  focal  areas  of  degeneration  he  noticed  diffuse  areas  of 
degeneration  in  the  long  association  tracts  and  in  the  short  commissural 
fibers  that  pass  from  one  gyrus  to  another.  He  calls  attention  to  the  fact  that 
the  gray  matter  shows  involvement  of  a  focal  nature  also,  the  cells  of  the 
marginal  gray  layer  being  principally  involved. 

REPORT  OF  CASES. 

Technic. — The  following  report  is  based  on  the  study  of  four  cases.  In  each  case 
the  brain  and  spinal  cord  had  been  fixed  in  formaldehyd  solution  and  cut  in  the  frontal 
plane.  Blocks  of  tissue  about  5  mm.  in  thickness  were  taken  from  each  of  the  fol- 
lowing regions:  (1)  left  motor  area;  (2)  middle  of  pons;  (3)  middle  of  medulla; 
(4)  cervical  region  of  cord;  (5)  dorsal  region  of  cord;  (6)  lumbar  region  of  cord 
In  addition,  sections  were  also  taken  in  some  cases  from  the  right  motor  area,  the  left 
internal  capsule,  and  the  peduncles.    These  were  selected  because,  macroscopically  they 

Page    iVI 


RANSOHOFF  MEMORIAL  VOLUME 


seemed  to  offer  promising  material  for  study.  These  blocks  were  then  mordanted, 
embedded  in  parlodion,  cut,  under  alcohol,  into  sections  25  microns  in  thickness  and 
stained  by  the  Weigert  method.  Those  stained  with  cresylecht-violet,  had  formalin 
fixation  and  paraflin  embedding  and  were  cut  into  sections  6  microns  in  thickness. 
Some  of  the  sections  were  also  stained  with  hematoxylin  and  eosin. 

Case  1  (Necropsy  15-106).  History. — O.  D.,  a  white  man,  aged  75,  was  admitted 
to  the  psychopathic  department,  Boston  State  Hospital,  September  27,  1915.  He  was 
mentally  confused  and  had  hallucinations  and  delusions  of  various  kinds. 

Family  History. — The  family  history  is  entirely  negative.  There  is  no  history  of 
nervous  or  mental  diseases  in  any  of  the  collaterals. 

Personal  History. — The  patient  was  born  in  Germany  and  had  the  ordinary  diseases 
of  childhood.  He  had  a  severe  attack  of  rheumatism  sometime  between  the  ages  of 
50  and  60  years.  About  four  or  five  years  ago  he  began  to  have  bladder  difficulties. 
He  left  school  at  the  age  of  15  and  spent  the  next  twenty-six  years  at  sea.  He  then 
came  to  this  country  and  worked  steadily  for  a  ship  concern  until  the  onset  of  the 
present  illness,  which  prevented  him  from  performing  his  duties  properly.  His  daughter 
stated  that  he  left  his  work  because  his  mind  gave  out  and  because  he  had  dizzy  spells 
and  would  fall  on  the  street.  His  condition  gradually  became  worse  and  he  had  begun 
to  dislike  people,  preferred  to  stay  alone,  was  irritable  and  ugly.     He  was  always  com- 


Fig.  1  (Case  1).  Section  of  left  motor  area,  showing  areas  of  degeneration  in 
close  proximity  to  the  blood  vessels.  One,  in  the  upper  right  hand  corner,  is  at  the 
point  of  bifurcation  of  a  capillary.  In  the  upper  left  hand  corner  a  focus  of  degen- 
eration is  seen  surrounding  blood  vessels.  \\  eigert's  myelin  sheath  stain.  Magnified 
about  40  diameters. 

plaining  and  found  fault  with  everything.  He  had  delusions  of  persecution.  His 
daughter  had  become  afraid  of  him  because  of  his  ugliness.  For  the  past  three  years 
he  had  been  very  pale  and  complained  of  numbness  of  the  feet.  However,  he  did  not 
drag  his  feet. 

Ten  weeks  before  admission,  the  patient  fainted  and  afterward  had  a  chill,  a 
period  of  vomiting  and  later,  fever  which  reached  102  F.,  after  which  he  had  a  peculiar 
cold  period.  It  seems  that  the  mental  confusion,  hallucinations,  rambling  and  inco- 
herent talk  have  chiefly  developed  since  the  onset  of  this  attack  of  chill,  vomiting  and 
fever.  Previously  he  had  always  been  constipated  but  during  this  bed-ridden  period 
there  was  diarrhea  and  he  had  no  control  of  rectum  or  bladder. 

His  hallucinations  varied.  At  one  time  he  saw  a  man  in  the  room  with  him, 
sitting  with  his  hat  on  ;  at  another  time,  he  saw  trucks  and  a  steamer  in  his  room.  At 
times  he  feared  that  he  was  going  to  be  put  down  into  the  cellar,  and  at  other  times 
he  thought  he  was  being  kept  there.    He  also  had  periods  of  memory  defect. 

E.raiiiiiiation. — On  examination,  the  face  was  seen  to  be  puffy  and  pasty  and  the 
skin  unduly  pale.     There  was  a  sytolic  murmur  at  the  apex  which  was  feebly  trans- 

Pagc  -'W 


LOUIS  A.  LUKIE 


Fig.  3  (Case  1).     A  so-tailed  Lichtheim  plaque  in  the  left  internal  capsule.     Wei- 
gert's  myelin  sheath  stain. 


RANSOHOFF  MEMORIAL  J'OLUME 


mitted  to  the  axilla.  The  aortic  second  sound  equaled  the  pulmonic  second  sound.  The 
pulse  was  regular  and  of  good  volume.  The  blood  pressure  was:  systolic,  130; 
diastolic,  70.  The  breath  sounds  were  faint  and  crepitant ;  rales  were  heard  all  over 
the  back  and  front.  The  liver  was  enlarged  but  not  tender.  The  spleen  was  not  pal- 
pable. 

Neurologic  examination  showed  normal  reacting  pupils.  The  fundi  could  not  be 
examined  on  account  of  the  patient's  restlessness.  The  triceps  and  biceps  were  present 
and  equal  on  both  sides.  The  abdominal  reflexes  were  only  obtained  in  the  left  inguinal 
region.     Both   knee  jerks   were   absent.      The   same   was   true   of   the   Achilles   reflex. 


Fig.  4  (Case  1).  Here  the  miliary  foci  described  by  Preobrajcnsky  are  very 
conspicuous.  The  contrast  between  them  and  the  larger  so-called  Lichtheim  foci, 
three  of  which  are  also  shown  in  this  picture,  is  very  striking.  The  foci  of  Proebra- 
jensky  are  much  smaller,  more  numerous  and  more  sharply  defined  than  the  Lichtheim 
plaques.  Although  not  shown  in  this  photograph,  in  a  good  many  cases  an  undamaged 
nerve  fibril  may  be  seen  traversing  a  small  focus.  Weigert's  myelin  sheath  stain  of 
pons. 

There  were  no  Babinski,  Gordon  or  Oppenheim  reflexes.     There  was  no  ankle  clonus. 
The  deep  sensibilities  were  not  tested  because  the  patient  could  not  co-operate. 

The  urine  showed  a  slight  trace  of  albumin  and  an  occasional  red  blood  corpuscle, 
and  a  few  granular  casts  and  a  rare  hyaline  cast.  The  blood  Wassermann  reaction  was 
negative.  Examination  of  the  spinal  fluid  showed  the  following:  Fluid,  clear; 
albumin,  +  +  +  ;  globulin,  +  +  ;  cells,  4 ;  small  lymphocytes,  100  per  cent.  Colloidal 
gold  chlorid  test,  000000000  0.  Blood  Examination  :  This  revealed  the  follow- 
ing: Hemoglobin,  30  per  cent.  (Sahli)  with  a  color  index  of  1.66;  red  blood  cells, 
2,528,000;  white  blood  cells,  4600.    A  differential  count  (100  cells)  gave  polymorphonu- 

Page  Wi 


LOUIS  A.  LURIE 


clear  leukocytes,  71  per  cent.:  small  lymphocytes,  16  per  cent.:  large  lymphocytes,  10 
per  cent. :  eosinophils,  3  per  cent. 

There  is  a  great  variation  in  the  size  of  the  red  Wood  cells  with  a  large  percen- 
tage of  macrocytes.     Poikilocytosis  is  marked.     No  achromia. 

Course. — Septemher  28 ;  Patient  had  heen  lying  quietly  all  day  in  a  semi-comatose 
condition.  He  does  not  comprehend  questions,  rarely  speaks,  and  when  he  does,  cannot 
answer  questions  relevantly.  His  mind  wanders  deliriously,  calling  for  ".Annie"  and 
telling  fahulous  tales. 

Septemher  30:  Condition  the  same.  The  skin  is  very  pale  and  lias  a  slight  lemon 
yellow  tint.  Both  knee  jerks  and  Achilles  are  absent.  All  the  toes  were  drawn  up  on 
stroking  the  sole  of  the  foot  and  in  testing  for  Oppenheim's  sign. 

October  1  :  The  patient  has  continued  in  the  same  low  grade  semiconscious  semi- 
delirious  condition  previously  noted.     He  continues  to  call  deliriously  for  "Annie,"  hut 


Fig"  5  (Case  1).  .Another  view  of  a  different  section  of  the  pons.  The  relationship 
of  the  large  plaques  of  degeneration  to  the  blood  vessels  is  very  clearly  shown.  Here 
we  see  again  the  formation  of  an  area  of  degeneration  at  the  bifurcation  of  a  capillary. 
A  large  number  of  the  smaller  foci  are  also  present.     (.Weigert  method.) 

otherwise  makes  practically  no  intelligent  remarks,  occasionally  rambling  about  "the 
boat."  The  yellowish  tint  of  the  skin  is  more  marked.  Moist,  bubbling  rales  could 
be  heard  all  over  the  chest.     Patient  failed  rapidly  and  died  early  in  the  afternoon. 

Necro[>sy. — This  was  performed  six  hours  after  death.  The  body  is  that  of  a  well 
built  and  nourished,  white  man,  176  cm.  in  length.  The  skin  is  waxy  gray  with  a 
slight  yellowish  cast.  There  is  a  faint  edema  of  the  lower  legs  and  some  atrophy  of 
the  left  thigh.  The  pupils  measure  5  mm.  in  diameter  and  are  equal.  There  is  a 
superficial  decubitus  over  the  sacrum.     Rigor  mortis  is  faintly  present. 

Page  S'jr, 


RAXSOHOFF  MEMORIAL  VOLUME 

\'entral  Section  :  The  fat  is  lemon  yellow  in  color  and  nicasnres  2  cm.  over  alnlo- 
men  and  1  cm.  over  thorax.  Tlie  spleen  is  adherent  to  the  external  lateral  surface. 
The  appendix  above  the  pelvic  brim  measures  7  cm.  in  length.  The  bladder  is  dis- 
tended and  the  intestines  somewhat  injected.  The  diaphragm  arches  to  the  fourth  rib 
on  the  right  side  and  to  the  fifth  interspace  on  the  left  side.  The  gall-bladder  is  dis- 
tended and  contains  many  stones. 

Thorax :  The  bone  marrow  is  yellowish  pink  in  the  sternum.  There  is  no  free 
fluid  in  either  pleural  cavity,  hut  there  are  adhesions  at  the  apex  of  the  right  lung. 
The  pericardium  is  heavily  loaded  with  fat.  The  apex  of  the  heart  is  in  the  fifth 
mterspace. 

Heart:  Weight,  453  gm.  The  epicardial  fat  is  fairly  abundant.  The  descending 
branch  of  the  left  coronary  shows  sclerosis.  The  right  coronary  and  circumflex  arter- 
ies show  constrictions  with  calcifications.  Every  valve  is  thickened,  particularly  the 
aortic  which  shows  distortion  of  the  cusps.  There  are  some  vegetations  which  are 
calcified  around  the  origin  of  the  left  coronary  in  the  internal  surface  of  the  aorta. 


Figs.  6,  7,  8  (Case  1.)  Sections  of  the  cervical,  dorsal  and  lumbar  regions  of  the 
.spinal  cord.  The  degeneration  of  the  posterior  columns  is  marked.  This  degenera- 
tion is  only  moderately  severe  in  the  lumbar  region,  but  becomes  progressively  worse 
in  the  upper  portions  of  the  cord.  It  reaches  its  climax  in  the  cervical  region.  Here, 
the  destruction  is  seen  to  be  very  severe.  Within  the  area  of  degeneration,  large, 
jagged  holes  are  present.  This  is  in  marked  contrast  to  tabes  dorsalis.  In  the  latter 
condition,  the  degeneration  of  the  posterior  columns,  as  a  rule,  is  greater  in  the  lumbar 
region  than  in  the  cervical  region.  The  degeneration  in  the  lateral  columns,  which  as 
a  whole  is  much  less  than  in  the  posterior  columns,  increases  in  intensity  from  above 
downward.  The  posterior  roots  in  the  lumbar  section  show  evidences  of  degeneration. 
The  hole  seen  in  the  lateral  column  of  each  section  has  been  made  to  mark  the  right 
side  of  the  cord.  This  applies  to  all  the  following  photographs  of  the  cord.  Weigert's 
myelin  sheath  stain  (X  10). 

The  myocardium  is  pinkish  gray  in  color  and  contains  multiple  white  streaks  measuring 
from  O.S  to  0,6  cm.  in  extent. 

Lungs:  Weight — left  lung,  385  gm. ;  right,  1200  gni.  The  right  lung  pits  on 
pressure,  but  is  crepitant  for  the  most  part.  There  is  a  slight  thickening  of  the  pleura 
at  the  apex.     The  bronchi  are  reddened  and  show  frothy  fluid  adherent  to  mucus. 

The  left  lung  has  a  collapsed  area  in  the  lowest  part  of  the  upper  lobe  and  in  the 
posterior  part  of  the  lower  lobe.  Section  of  this  shows  it  to  be  somewhat  redder  but 
not  wetter  than  usual.  The  bronchi  are  reddened  but  the  peribronchial  lymph  nodes 
are  not  enlarged. 

Page  200 


LOUIS  A.  LURIE 


Spleen  :  Weight,  165  gm.  There  are  two  fetal  lobulations  on  the  lower  border. 
The  capsule  is  somewhat  thickened  and  wrinkled.  The  pulp  is  red  and  watery,  and 
letracts  on  section.  The  trabeculae  are  increased  and  the  malpighian  bodies  are 
numerous. 

Adrenals :  They  are  embedded  in  fat  and  are  large.  On  section  they  show  marked 
mottling  of  cortex  and  medidla  with  yellow  and  red.  The  medulla  is  scarcely  to  be 
differentiated  from  the  cortex. 


Figure  8 

Kidneys :     These  are  deeply  embedded  in  fat.    The  capsule  strips  with  difficulty. 

Liver :  Weight,  1800  gm.,  and  has  a  yellowish  pink  color.  The  capsule  is  slightly 
thickened  and  there  is  a  focal  area  of  adhesion  to  the  diaphragm.  Section  shows  a 
fairly  pale  homogeneous  substance.     The  gall-bladder  contains  forty-eight  stones. 

Pancreas;  The  splenic  artery  is  tortuous,  markedly  sclerosed  and  calcified.  Every 
level  of  the  pancreas  examined  shows  fat  replacement  in  varying  amounts. 

Page  Hit 


RAXSOHOPF  MEMORIAL  VOLUME 


Gastro-Iiitestinal  Tract:  Section  of  stomach  shows  the  wall  somewhat  thickened 
and  glossy.  Xo  rugae  are  present.  Yellow  mucus  drips  from  the  surface.  There  is 
nothing  of  note  in  the  intestinal  tract. 

Special  Examination:  The  bone  marrow  of  the  left  femur  was  inspected,  and 
found  to  be  raspberry  red  in  color. 

Brain  :  The  dura  is  very  adherent,  but  not  particularly  thickened.  The  superior 
surface  of  the  brain  generally  is  firmer  than  normal.  The  convolutional  pattern  is 
rich.     The  pia  mater  is  not  thickened  except  slightly  in  the  sulci  over  the  vertex. 

Base  of  brain  shows  a  small  aneurysm  in  the  middle  part  of  the  left  posterior 
communicating  artery.  The  fourth  ventricle  shows  clear  granulations.  The  brain 
weight  is  1100  gm.,  which,  according  to  Tigges'  formula,  shows  a  loss  of  308  gm.  The 
cord  shows  minute  specks  of  translucency  in  the  middle  of  the  posterior  columns. 


CoLLOiD.AL  Gold  Chi.orid  Re.^ction. 


1|2I.^14!SI6|7!8|9|10 

Cortex  

r2'2'2'2'3'n'OiO 

Bloodv 

Right  base  

1  2  n  1  1 11 0  010 

Bloody 

Left  base  

Mil  1  1  imVO'O 

Bloodv 

Third  ventricle* 

(1  II  iMi  II  (1  (10  0'  0 

Spinal  fluid   

1  M  ,  1  M  M  M  1  1  1  (1  1 1    0 

Pericardial  fluid  

(HMMI   1    1    1    2  2    .^ 

Histologic  Examinations. — IVeiacrt  Sectinns — Left  Motor  Area  ■  Macroscopicallv, 
one  sees  a  cross-section  of  a  very  large  blood  vessel  with  thickened  walls.  Surround- 
ing it,  in  the  medullary  substance,  is  a  very  large  area  of  softening  which  shades  off 
gradually  into  the  surrounding  normal  tissue.  On  microscopic  examination,  this  area 
of  softening  is  seen  to  be  composed  of  destroyed  nerve  fibers,  with  here  and  there 
small  patches  of  neuroglia  and  intact  nerve  fibers.  The  entire  part  appears  cribriform 
owing  to  the  presence  of  many  large  vacuoles,  some  of  which  have  apparently  run 
together  to  form  large  cavity-like  spaces.  In  the  medullary  portion,  the  blood  vessels 
are  thickened,  the  perivascular  spaces  are  dilated  and  in  a  great  many  instances  there 
is  a  thinning  out  of  the  myelin  sheaths  in  their  immediate  neighborhood.  In  many 
cases,  this  destructive  action  has  gone  on  to  complete  degeneration  so  that  irregularly 
circumscribed  areas  which  vary  in  size  and  structure  have  been  formed.  Some  are 
filled  with  debris  and  crossed  by  a  few  undegenerated  nerve  fibers,  while  others  are 
clear  and  hyaline-like  in  appearance.  At  the  bifurcation  of  one  of  the  capillaries  there 
is  a  so-called  Lichtheim  focus.  In  the  cortical  area  the  blood  vessels  are  numerous 
and  have  very  thick  walls.  Some  are  seen  to  be  ruptured.  The  perivascular  spaces 
are  greatly   distended. 

Internal  Capsule:  Here  there  are  also  vascular  changes  both  in  the  gray  and  white 
matter.  Many  plaques  of  different  sizes  and  shapes  are  seen  surrounding  the  blood 
vessels.  The  perivascular  spaces  are  uniformly  distended.  In  a  small  portion  of  the 
medullary  substance  one  can  see  a  few  of  the  miliary  foci  described  by  Preobrajensky. 

Pons :  The  most  striking  feature  in  this  section  are  the  miliary  foci  of  Preobra- 
jensky. They  are  very  numerous  and  confined  entirely  to  the  medullary  portions  and 
are  most  numerous  in  the  center.  Practically  all  are  of  uniform  shape  but  not  of  uni- 
form size,  some  being  three  times  as  large  as  others.  The  smallest  are  about  the  size 
of  small  lymphocytes.  They  are  fairly  definitely  circumscribed  and  have  a  punched 
out  appearance.  In  many,  an  undamaged  nerve  fibril  may  be  seen  passing  through 
the  destroyed  area.  In  addition  to  these  miliary  foci  of  Preobrajensky  there  are  quite 
a  number  of  well  defined  Lichtheim  plaques.  These  bear  a  close  relationship  to  the 
blood  vessels. 

Cord :  With  the  unaided  eye  one  can  see  a  distinct  circumscribed  degeneration  of 
the  column  of  GoU.  In  the  cervical  region,  this  has  proceeded  to  apparent  cavity  for- 
mation. The  degeneration,  although  still  sharply  defined  in  the  thoracic  region,  becomes 
less  and  less  marked  as  we  pass  to  the  lumbar  region.  The  reverse,  however,  is  true 
of  the  lateral  columns.  Here  the  degeneration,  which  is  much  slighter  than  in  the 
posterior  columns,  increases  from  above  downward.  On  microscopic  examination,  we 
see  that  the  column  of  Goll  is  practically  entirely  destroyed.  Several  large  spaces  with 
irregular  jagged  edges  are  conspicuous.  Smaller  vacuoles  are  numerous.  Here  and 
there  are  evidences  of  small  hemorrhages.    The  blood  vessels  are  intensely  congested. 

Cresylccht-Viotet  Sections—Left  Motor  Area:  The  pyramidal  cells  appear 
shrunken  and  granular.  Many  of  the  pericellular  spaces  are  filled  with  a  large  num- 
Page  298 


LOUIS  A.  LURIE 


her  of  satellite  cells.  The  perivascular  spaces,  especially  those  of  the  cortical  area,  are 
distended. 

Internal  Capsule:  Here  and  there  are  small  islands  of  sclerotic  tissue,  apparently 
not  related  to  the  blood  vessels.  The  pyramidal  cells  are  uniformly  shrunken,  irreg- 
ular in  outline,  and  in  a  great  many,  the  nucleus  is  displaced.  Some  satellitosis  is 
present.  From  one  pericellular  space,  the  nerve  cell  had  entirely  disappeared  and  its 
place  is  occupied  by  live  satellite  c^lls. 

Pons:  Small,  clear,  oval  areas  corresponding  in  size  and  position  to  the  miliary 
foci  of  Preobrajenskv,  seen  in  the  Weigert  section  of  the  pons,  are  also  present  here. 
In  the  gray  matter  there  are  many  small  patchy  areas  of  degeneration.  The  nerve  cells 
are  not  as  noticeably  abnormal  as  those  of  the  preceding  sections. 

Medulla  :  Pigmentation  of  the  nerve  cells  is  marked.  The  perivascular  spaces  are 
tremendously  distended  and  filled  with  debris.  Large  areas  of  degeneration  are  present 
in  the  white  matter.  The  pyramidal  tracts  are  full  of  vacuoles.  Two  types  of  glia  cells, 
diflering  principally  in  size,  were  observed.  The  larger  ones,  in  all  probability,  sirnply 
represent  more  mature  forms.  They  are  profusely  distributed  over  the  entire  section, 
but  more  particularly  in  the  region  of  the  olivary  nuclei. 

Cord :  The  posterior  columns  contain  numerous  thin  walled  capillaries  which  are 
surrounded  by  large  amounts  of  glia  cells  and  fibers.  The  glia  replacement  cells  are  of 
comparatively  large  size  and  of  the  stellate  type.  An  occasional  undegenerated  or  only 
partially  degenerated  nerve  fiber  is  seen.  The  increase  in  the  number  of  blood  vessels 
is  most  noticeable  in  the  dorsal  portion  of  the  cord.  The  nerve  cells  show  various 
changes.  Some  are  very  much  shrunken  and  irregular  in  outline ;  others  contain  numer- 
ous variously-sized  granules;  still  others  are  swollen  and  contain  a  large  amount  of 
yellow  pigment.  Pigmentation  is  present  both  in  the  anterior  and  posterior  horn  cells, 
but  occurs  more  frequently  and  uniformly  in  the  former.  This  pigmentation  differs 
from  that  normally  found  in  the  cells  of  persons  of  advanced  years,  in  that  it  is 
diffuse,  somewhat  granular  and  not  clumped  at  one  pole  of  the  cell  body.  In  these 
cells,  the  pigment  is  centrally  located  and  apparently  has  pushed  the  protoplasmic 
substance  to  the  extreme  periphery  of  the  cell.  In  some  of  the  cells,  the  nucleus  is 
displaced  to  one  side  and  stains  poorly. 

Case  2  (Necropsy  16-59).  Historv.—C.  C.  a  white  woman,  aged  54.  Was  com- 
mitted to  the  Boston'  State  Hospital,  April  25,  1916,  with  the  diagnoses  of  pernicious 
anemia  and  symptomatic  psychosis. 

Family  History. — Her  mother  died  at  the  age  of  fifty  of  tuberculosis.  Of  six 
siblings,  two  have  died  of  tuberculosis;  one  is  now  in  a  hospital  suffering  from  tuber- 
cular trouble;  one  (a  sister)  is  excessively  alcoholic  and  has  seizures  with  unconscious- 
ness, and  one  died  in  infancy. 

Personal  History. — The  patient  was  born  at  Salem,  Mass.,  in  1862.  Her  education 
was  limited  but  she  was  able  to  read  and  write.  She  drank  a  little  beer  and  smoked 
cigarets  for  about  a  year.  She  formerly  used  snuff.  Her  sexual  habits,  as  far  as 
could  be  ascertained,  were  normal.  She  was  never  very  cheerful,  and  many  times 
greatly  depressed.  She  was  somewhat  obstinate,  but  in  many  ways  showed  that  she 
could  be  very  sympathetic  and  kind.  She  was  known  to  be  hypochondriacal  and  appre- 
hensive. She  was  a  good  housekeeper,  was  sociable  and  made  friends.  Her  first  mar- 
riage occurred  when  she  was  eighteen  years  old.  By  that  husband  she  had  one  child, 
who  died  at  the  age  of  three  of  "water  on  the  brain."  .\t  the  age  of  thirty-six  she  was 
again  married,  but  by  this  marriage  she  had  no  children  and  no  miscarriages.  Since  the 
second  marriage  she  has  led  a  very  lonesome  life. 

Medical  History. — In  childhood  she  was  at  the  Salem  Hospital  because  of  anemia. 
According  to  the  statements  of  her  acquaintances,  she  has  always  been  pale.  She 
always  claimed  that  she  was  a  spiritualist  and  "could  see  dead  people."  Early  in  1915 
she  went  to  the  Eye  and  Ear  Infirmary  because  she  thought  that  she  had  cancer  of  the 
throat.  In  May  of  that  year  she  was  for  nearly  three  weeks  a  patient  at  the  Massa- 
chusetts General  Hospital  with  what  was  diagnosed  as  pernicious  anemia.  At  that 
time  she  was  irrational  and  had  visual  hallucinations.  She  saw  animals  and  would 
point  her  fingers  at  imaginary  objects.  She  walked  unsteadily  and  fell  frequently  but 
never  lost  consciousness.  Sometimes  she  had  complete  loss  of  vision  for  a  few  min- 
utes. Until  a  year  previous  to  this  attack,  the  patient  was  able  to  do  her  housework. 
Six  weeks  ago  she  became  much  worse ;  very  excitable,  swore  and  used  obscene  lan- 
guage. Recently  she  carried  on  an  imaginary  conversation  with  her  deceased  daugh- 
ter. She  has  also  turned  against  her  niece  and  niece's  little  girl  of  whom  she  has  been 
very  fond.  On  occasions  she  would  "jump  out  of  bed  at  people."  There  were  no 
homicidal  or  suicidal  tendencies. 

Physical  Examination. — The  patient  was  a  well  developed  and  well  nourished 
woman  of  fifty-four.     Her  face  was  of  a  striking  pallor  with  a  lemon  yellow  tinge. 

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RANSOHOFF  MEMORIAL  VOLUME 


The  mucosae  were  very  pale.  There  was  a  harsh  systolic  murmur  at  the  apex  that  was 
transmitted  upward  to  the  axilla.  The  liver  was  enlarged  hut  not  tender.  The  spleen 
was  palpahle  in  the  left  hypnchoiidrium  and  the  dullness  extended  to  3  cm.  above  the 
umbilical  line.     The  blond  pressure  readings  were:     systolic,  105:  diastolic,  45. 

Neurologic  l'..rniiiiiiali"ii_ — TIk-  pupils  were  equal  and  regular.  They  reacted  well 
to  accommodation  but  xery  sluguisbly  to  light.  There  was  no  nystagmus  or  strabismus. 
The  tongue  protruded  in  the  midline  and  appeared  very  anemic.  The  arm  reflexes 
were  all  hyperactive.  There  was  hyperesthesia  of  'the  lower  extremeties.  The  knee 
jerks  were  equal  but  sluggish:  the  Achilles  active  and  equal,  and  the  plantars  hyper- 
active. No  Babinski,  Gordon  or.^Oppenheim  reflexes  were  obtained.  There  was  no 
ankle  clonus. 

A  formal  mental  examination  could  not  be  made  on  account  of  her  mental  state. 
The  patient  appeared  to  be  in  a  dazed,  half  asleep  state'.  It  was  difficult  to  get  her 
to  comprehend  questions,  but  when  her  attention  was  gained  she  usually  answered  the 
questions  fairly  well.     \\  hen  asked  where  she  was  born,  she  delayed  before  answer- 


Fig.  9  (Case  2).  Weigert's  myelin  sheath  stain  of  left  motor  area  showing  small 
foci  of  degeneration  and  one  larger  area  in  intimate  relatiousliip  with  the  neighboring 
blood  vessels. 


ing,  then  asked  what  the  question  was.  Slie  finally  said  that  she  was  born  in  Salem. 
She  did  not  know  how  long  she  had  lived  there.  She  answered  questions  as  if  very 
weary  and  gave  the  impression  that  the  incorrect  answers  were  due,  in  part,  to  lack 
of  effort.  She  persisted  in  the  feeling  that  her  niece  had  intended  to  injure  her  and 
refused  to  see  her.  Her  condition  gradually  grew  worse  and  she  was  less  and  less 
easily  aroused.     Twelve  days  after  her  admission,  she  died. 

Wassermann  Reaction  :     Serum,  negative. 

Blood  Examination:  Hemoglobin  less  than  10  per  cent.  ( Sahli  I  ;  color  index, 
1.6;  red  blood  cells,  780,000;  white  blood  cells,  4,700;  polymorphonuclear  leukocytes, 
GO  per  cent. ;  small  lymphocytes,  ,32  per  cent. ;  large  lymphocytes,  8  per  cent.  The  red 
blood  cells  showed  marked  anisocytosis  and  poikylocytosis,  and  some  achromia.  There 
was  a  large  number  of  microcytes  and  macrocytes.  No  stipling  or  nucleated  reds 
were  seen. 

A  later  blood  examination  showed  hemoglobin  less  than  10  per  cent.  (  Sahli )  ;  red 
blood  cells,  550,000;   white   blood  cells,  4,500;   polymorphonuclear   leukocytes,  01    per 

Page  .100 


LOUIS  A.  LURIE 


cent. ;  small  lymphocytes,  34  per  cent.  :  large  lymph, 
eosinophils,  1  per  cent.:  mast  cells,  1  per  cent.  T\v 
were  seen.  The  red  blood  cells  shuwcd  iii.irkdl  \ 
were  very  many  small  cells  Init  tin-  inai'ini\  w .  i  r 
index  was  increased.  There  was  n..  aclnniiii.i  aii'l 
sional  cells  showed  marked  polychrcjinalophilia  and  < 
'  tipling 

\  I  l^^\  Pi  iln  )/— The  body 
wrman  1S7  cm  m  length  F  i,,(  r  i 
are  palpable  The  skm  is  km  n  \  1 
SIX  hours  after  death      Tli     |  ii|   1 

Ventral  Section  The  il  1  nm: 
fat  being  bncht  lemon  m11   w       I  li 


i-tes.  3  per  cent.;  transitionals,  0: 
norninlilasts  and  one  megaloblast 

lain  III    111    '~i/c   and    shape.     There 
irrii,\tis  ,ind  tile  aMTagc  volume 

asioiial  cells  showed  very  marked 


s  that  of  a  well  developed  pi3rl>  n  urished 
rtis  is  not  present  No  superhcnl  hmph  nodes 
i\  111  color  The  necrops^  was  perf  irincd  thirty- 
|im1  and  regular  and  0  4  cm  m  dnmcttr. 
I  It  IS  bright  ^ellow  the  thoracic  an  1  mental 
\    I   1     12  tm    lelrw   the  ensiform  nrtilage.     The 


Fig     10    (Case 
method      ffere 
midullarv  substan 


spleen  is  not  encased  in  adhesions.  The  appendix  is  retrocecal  and  adherent  to  the 
cecum.  The  diaphragm  arches  to  the  lower  border  of  the  fourth  rib  on  the  right  and 
to  the  lower  border  of  the  fifth  rib  on  the  left. 

Heart:  The  myocardium  of  left  ventricle  shows  tiger  lily  striations  with  here  and 
there  translucent  areas.     The  muscle  is  soft. 

Lungs  :  These  are  encased  in  adhesions.  The  cut  surface  is  grayish  brown  in 
color  at  the  apices.  In  the  lower  lobe  it  is  pinkish-yellowish-gray.  The  connective 
tissue  element  is  well  marked.  A  frothy,  grayish  fellow,  thick  fluid  is  scraped  from  the 
cut  surface. 

Abdomen :  The  spleen  weighs  185  gm.  and  is  of  firm  consistency,  with  a  shiny 
surface.  It  is  purplish  brown  in  color.  The  capsule  is  not  thickened;  the  trabeculae 
are  prominent  and  the  nialpighian  bodies  appear  as  pin  points. 

Kidneys;  These  showed  cystic  areas  on  the  lateral  edge.  The  capsules  stripped 
easily. 

Liver:  This  weighs  L560  gm.  It  is  shiny,  mottled  and  of  yellowish-brown  color. 
The  capsule  in  general  is  not  thickened.     It  is  of  firm  consistency. 

Pancreas:     Pale;  otherwise  there  is  nothing  of  note. 

Gastro-lntestinal :  The  stomach  is  pale,  glassy  and  atrophic  in  appearance  near 
the  cardiac  end. 

Head;  The  skull  tables  show  a  symiiu-lrical  tliickening.  There  are  slight  patches 
of  endostosis  in  the  frontal  region. 


RANSOHOFF  MEMORIAL  VOLUME 


Superior  Surface  of  Brain  :  There  is  no  apparent  atrophy  and  it  is  firm  to  the 
touch.  There  are  inequalities  between  the  first  and  second  frontals  and  between  the 
right  and  left  prefrontals. 

Base  of  Brain  :  The  basilar  artery  is  small  and  no  sclerosis  in  the  circle  of 
Willis  could  be  seen.  There  is  a  slight  thickening  of  the  pia  around  the  third  nerves, 
otherwise  the  cranial  nerves  show  no  abnormalities.  The  mammillary  bodies  are  flat- 
tened. The  brain  is  pale.  The  fourth  ventricle  is  clear.  A  pressure  ring  cerebellum 
is  noted.  In  the  left  base  the  fluid  is  yellow.  This  also  applies  to  the  corte.x.  How- 
ever, neither  the  right  base  nor  the  third  ventricle  showed  this  condition.  The  spinal 
fluid  was  mixed  with  blood.  The  brain  weighed  1,175  gm.,  which  according  to  Tigges' 
formula  gives  a  loss  in  weight  of  81  gm. 

Colloidal  Gold  Chlokid  Reaction. 

~"  1|2|3|4|5|6|7|8!9|10 

Cortex   4|S15|5|SI3|3|2|1 1  0 


Left  base   

4!4\Si,T  5  5'.' 

!  i  r  n 

Right  base  

1;4',^  ^  .\  -?  } 

;  _'  1  0 

Third  ventricle  (blood  stained) 

oio'i  1  iJ  :• 

12  1    0 

Spinal  fluid   (blood  stained) 

O'O'l  4  -  ^  ^ 

\  ^  ^  '• 

Pericardial  fluid  

O'Oii  1  _',^  .= 

r-  ?    ,1 

Histological  Examination. — Weigert  Section — Left  Motor  Area. — Small  foci  of 
degeneration  resembling  those  described  by  Preobrajensky  are  noticed  in  the  subcort- 
ical region.  These,  however,  are  not  numerous.  There  are  also  some  larger  areas  of 
degeneration  that  are  in  close  relation  to  the  blood  vessels. 

The  cortical  perivascular  lymph  spaces  are  distended  and  here  and  there  are  asso- 
ciated with  small  areas  of  degeneration. 

Pons :  Here  we  also  see  miliary  foci  of  Preobrajensky.  Init  these,  unlike  those 
described  in  Case  1,  are  more  numerous  in  the  peripheral  portions  of  the  medullary 
substance.  The  myelin  is  thinned  out  in  many  places  and  in  many  instances  this  has 
gone  on  to  complete  degeneration.  Three  Lichtheim  plaques  were  counted  which  were 
in  intimate  contact  with  the  blood  vessels.  In  addition,  two  sharply  defined  areas  of 
degeneration,  involving  entire  tracts,  are  present.  These  are  also  seen  in  the  sections 
of  the  pons  stained  with  cresylecht-violet  and  are  more  fully  described  under  the  latter 
heading.     The  gray  matter  showed  practically  no  involvement. 

Medulla:  The  white  matter  showed  but  slight  involvement.  Discretely  scattered 
between  the  fibers  of  the  raphe  were  small  foci  of  degeneration.  In  the  gray  matter, 
however,  it  was  not  uncommon  to  come  upon  distinct  areas  of  degeneration  in  the 
neighborhood  of  blood  vessels.  This  was  especially  true  of  the  dorsal  portion  of  the 
medulla. 

Cord :  In  the  left  lateral  column  of  the  cord,  in  the  cervical  region,  there  are 
several  foci  of  the  Lichtheim  type.  The  blood  vessels  which  are  rather  numerous  have 
greatly  thickened  walls.  In  the  lumbar  region,  there  are  patchy  areas  where  the  myelin 
is  thinned  out.     The  gray  matter  appears  normal. 

Cresylccht-Violct  Sections — Left  Motor  Area. — The  pyramidal  cells,  especially 
those  in  the  outermost  layer  of  the  cortex,  are  shrunken  and  irregular  in  outline,  the 
nucleus,  in  many  cases,  being  crowded  to  one  side.  In  others  it  is  entirely  absent. 
Satellite  cells  are  numerous.  Large  stellate  glia  cells  were  observed.  The  blood  vessels 
are  numerous  and  the  perivascular  lymph  spaces  are  uniformly  distended.  The  sub- 
cortical area  shows  no  large  areas  of  degeneration,  but  here  and  there  a  few  small, 
clear  areas. 

Pons:  Here  we  see  many  evidences  of  a  pathologic  process.  In  the  medullary  sub- 
stance there  are  numerous  sievelike  areas.  Here  the  destruction  of  the  nerve  fiber.s 
has  not  been  accompanied  by  any  considerable  increase  in  the  neuroglia  fibers,  thereby 
producing  the  cribriform  appearance.  One  also  notices  large  sclerotic  areas  which 
apparently  are  c..niii.,M(l  entirely  of  neuroglia.  These  hyaline-like  areas  involve 
entire  tracts  and  ,ii(  (Ir!iniiil\  circumscribed  by  fibers  of  other  tracts  which  evi- 
dently have  escaped  lie  hil;  iiufilved  in  the  destructive  process.  Furthermore,  these 
sclerotic  areas  arc  >\  niiiu  irn  ally  distributed  on  either  side  of  the  pons.  In  addition  to 
the  areas  just  described,  there  are  numerous  perivascular  areas  of  degeneration.  These 
vary  in  size  and  have  no  definite  margins,  but  shade  off  insensibly  into  the  surrounding 
tissue.  One  of  these  perivascular  areas  of  degeneration  extends  into  a  small  collection 
Page  SO'l 


LOUIS  A.  LURIE 


Fig.  11  (Case  2).  Another  section  of  the  pons.  Note  the  uneven  deniyelinization 
of  an  entire  tract.  The  destruction  has  progressed  very  far  in  the  center  vifhere  large 
sclerotic  areas  have  been  formed.  Compare  this  photograph  with  Figure  12,  which  is 
the  same  area  stained  with  cresylecht-violet. 


RAXSOHOFF  MEMORIAL  VOLUME 


of  nuclear  cells  which  also  show  evidence  of  pathological  involvement.  They  are  irreg- 
ular in  outline.  Many  are  shrunken  and  granular  and  some  show  a  diffuse  chroma- 
tolysis. 

In  the  larger  collections  of  gray  matter,  the  perivascular  spaces  are  distended  and 
here  and  there  one  sees  a  patchy  area  of  degeneration.  These,  however,  are  not  numer- 
ous. The  majority  of  the  nerve  cells  show  more  or  less  changes.  The  axonal  type  of 
degeneration  was  observed. 


m^. 


Kis.  1-  Case  l').  Same  area  of  pons  as  in  Fii;ure  11  st 
This  also  shows  the  uneven  degeneration  of  the  entire  tract 
of  degeneration  are  seen.     (X50.) 


Medulla:  In  the  white  matter,  there  are  streaky  patches  of  degeneration.  Vacuo- 
lization is  pronounced.  The  pyramidal  tra(t'~  Avw  no  changes.  Very  few  of  the  nerve 
cells  appear  normal.  The  majority  are  liiulil\  t;r.imilar  and  show  more  or  less  displace- 
ment of  the  nucleus.    Clear  areas,  that  appear  like  rifts  in  a  cloud,  are  scattered  about. 

Cord  :  Many  irregular,  pale  areas,  containmg  necrotic  tissue  and  surrounded  by 
neuroglia,  can  be  seen  in  the  lateral  columns.  In  some  cases,  the  neuroglia  cells  seem 
to  be  clumped  together.  This  is  also  met  with  but  to  a  much  lesser  extent  in  the  pos- 
terior columns.  The  cells  of  the  anterior  horns  are  bizarre  in  shape  and  contain  yellow 
pigment,  similar  to  that  described  in  the  preceding  case. 

Case  3  (Xecropsy  18-34).  History.^ — J.  H.,  a  white  boy,  aged  6  years  and  llj-i 
months,  was  admitted  to  the  Monson  State  Hospital,  January  IS,  1917,  with  the 
diagnosis  of  epilepsy. 

'This  case  will  be  icpoitcd  iiiojc  fully  in   a   laK-i    iiapui. 


LOUIS  A.  LURJE 


family  History. — Father  and  mother  are  living  and  well.  The  father  was  36  and 
the  mother  34  years  old  at  the  time  of  the  birth  of  the  patient.  The  patient  is  one  of 
sexen  children.  One  older  lirother.  who  was  an  epileptic,  died.  There  is  no  other  his- 
tory of  insanity  or  feeblemindedness  in  the  family.  .An  older  sister  of  the  patient  died 
of  pneumonia,  aged  two  months.  Three  older  brothers  are  living  and  well.  The  oldest, 
howexer,  had  conxulsions  when  teething  at  one  year  of  age  and  had  four  convulsions 
<hirMig  the  follow  mg  A  ear  He  was  then  circumcised  and  he  has  been  free  from  con- 
xulsions exti  smcc  Since  the  patient  was  born,  one  sister  has  died,  aged  six  weeks, 
idusL  unknown      fine  xounger  brother  is  well. 

Vijsi'iia!  IhsloiY — The  patient  had  a  normal  liirth  and  infancy  up  to  two  years, 
■ftluii  li(  li  1(1  his  Inst  ciinxulsion.  Teething  was  normal.  He  talked  at  one  year  and 
Hallvid  il  (lt\cii  niduths  He  has  had  no  exanthemas,  except  chickenpox.  He  went  to 
kindLr'jaitcn  and  lirst  yiadc,  passed  and  gi.t  along  as  well  as  the  other  children. 


.J 


Fig  13  (Case  2).  Cresylecht-violet  sections  of  the  pons.  Here  there  are  two  sieve- 
like  areas  of  degeneration  surrounding  two  blood  vessels.  This  shows  beautifully  the 
intimate  relationship  between  the  blood  vessels  and  the  "anemic  foci."  Evidently  in  a 
given  area,  some  of  the  nerve  fibers  succumb  to  the  toxic  action  sooner  than  others 
In  this  manner,  no  doubt,  the  cribriform  or  sievelike  areas  seen  above  are  reproduced. 
(X50.) 


Menial  Condition. — .Mthough  the  mother  states  that  the  patient  went  to  kinder- 
garten and  passed  the  tirst  year  in  graded  school,  he  is  defective  in  school  knowledge 
of  the  first  grade.  He  can  count  up  to  100,  but  can  write  only  the  initials  of  his  name. 
He  can  read  and  write  no  words  at  all.  He  reacts  normally  to  the  emotions  and  shows 
no  other  abnormal  reactions  except  an  apparent  memory  defect  for  daily  occurrences. 
He  behaves  rather  strangely  at  times,  apparently  not  realizing  just  where  he  is  going 
or  what  he  is  doing  when  out  with  other  boys.  He  starts  off  aimlessly  and  appar- 
ently need  supervision.  ISinet  tests,  however,  show  his  mental  age  to  be  6.1  years. 
.\ccording  to  the  Yerkcs-Bridges  scale  he  is  7.1  years  mentally.  His  first  seizure 
occurred  at  two  years  of  age.  According  to  the  mother's  statements,  the  patient  vvks 
in  a  baby  carriage  which  was  being  wheeled  by  a  young  girl  when  the  carriage  sud- 
denly tipped  over.  The  child  was  apparently  unhurt.  Eight  hours  later,  however,  he 
had  a  convulsion  which  the  mother  attributes  to  the  fall.    There  is  no  history  of  uncon- 

Pti^^  .Mr. 


RANSOHOFf  MEMORIAL  VOLUME 


tig.  14  (Case  2).  Another  part  of  tlie  sai 
which  surrounds  the  blood  vessels,  extends  into 
cells.     (X50.) 


section.     Here   the   degeneration, 
neighboring   collection   of  nuclear 


Big!  IS  (Case  2).  Weigert's  myelin  sheath  stain.  Section  of  the  cervical  region  of 
the  cord  showing  plaques  of  degeneration  in  the  lateral  columns.  The  hole  in  the 
right  lateral  column  has  been  artifically  produced  to  indicate  the  right  side  of  cord. 
(XIO.) 


LOUIS  A.  LURIE 


sciousness  or  apparent  injury  at  the  time  of  the  accident.  Since  that  time,  liowevcr, 
the  patient  has  had  seizures,  both  of  grand  mal  and  petit  ma!  type.  These,  further- 
more, have  been  increasing  in  frequency  of  late  and  at  present  occur  almost  daily. 

Physical  Examination. — The  patient  shows  no  marked  asymmetry.  Head  measure- 
ments:  circumference,  2Q  inches;  glabella  to  inion,  11  inches;  transverse,  10  inches. 
The  neurolo.gica!  examination  showed  nothing  abnormal.  The  blood  Wassermann 
reaction  was  negative. 

Course. — The  patient  remained  at  the  hospital  until  June  17,  1916,  and  during 
that  time  had  on  an  average  ten  convulsions  per  month.  He  gained  in  weight  and 
height,  but  had  made  little  or  no  progress  in  school.  He  had  an  attack  of  status  epilep- 
ticus  of  twenty-six  grand  mal  seizures.  He  was  readmitted  to  the  hospital  on  October 
20,  1917,  without  any  apparent  change  in  his  physical  condition.  He  had  had  an  attack 
of  status  epilepticus  while  home  on  a  visit.  A  second  Wassermann  test  was  reported 
negative.  After  readmission  he  had  less  seizures,  averaging  only  two  or  three  each 
month,  but  he  exhibited  a  marked  change  in  his  mentality.  He  attended  school  but  with- 
out making  any  progress.     .\t  times  he  would  play  and  associate  with  other  children. 


Fig.  16  (Case  3).  Section  of  the  left  motor  area  showing  numerous  foci  of  degen- 
eration which  vary  greatly  in  size.     W'eigert's  myelin  sheath  stain. 

sing  songs  which  he  had  committed  to  memory  and  appear  quite  normal.  At  other  times, 
lasting  for  periods  which  varied  from  a  few  hours  to  several  days,  he  would  be  very 
seclusive;  hide  himself  about  the  ward,  in  closets,  under  beds;  would  not  associate  with 
the  other  children,  but  would  be  found  sitting  alone  (|uietly  and  if  asked  the  reason  for 
so  doing  would  reply,  "Other  boys  are  rougli  and  intend  to  kill  me."  Very  often  he 
would  volunteer  the  information  that  he  was  .yning  U\  kill  himself  but  would  not  specify 
in  what  manner. 

There  was  no  marked  change  physically  or  mentally  until  .April  16,  1918,  when  the 
patient  was  noticed  to  be  suddenly  acutely  ill.  He  vomited  several  times,  complained 
of  headache,  and  there  was  a  slight  rise  in  temperature.  By  the  twenty-first  the  condi- 
tion had  somewhat  improved.  There  was  no  nausea  or  vomiting  and  the  patient  took 
liquid  nourishment  fairly  well.  The  skin  of  the  whole  body  had  a  marked  greenish, 
lemon  yellow  tint.  The  mucous  membranes  showed  marked  pallor.  A  blood  examina- 
tion showed  hemoglobin,  70  per  cent. ;  70,000  leukocytes  and  2,000,000  red  blood  cells. 
The  color  index  was  high,  namely,  1.75.  :\  differential  count  gave  polymorphonuclear 
leukocytes,  57  per  cent;  small  lymphocytes,  20  per  cent.;  large  lymphocytes,  21  per 
cent.;  transitionals,  1  per  cent.;  basophils,  1  per  cent.  A  differential  stain  showed  gran- 
ular degeneration  of  the  red  cells,  presence  of  nucleated  reds,  and  also  some  megalo- 
blasts. 

Page  301 


RAXSOHOFF  MEMORIAL  J-QLUME 


In  the  night  the  patient  was  very  restless  and  exhibited  a  marked  psychosis.  With 
his  finger  nails  he  tore  a  gash  in  the  perineum,  anterior  to  and  extending  into  the 
rectum.     He  also  scratched  his  face  and  hands  with  his  finger  nails. 

On  the  twenty-fourth  he  was  more  quiet  but  still  threatened  to  destroy  himself 
and  had  to  be  restrained.  The  skin  still  retained  the  same  peculiar  hue  and  there  were 
no  different  physical  signs.  Toward  evening  the  temperature  rose  to  103  F.,  and  early 
the  next  morning  the  patient  died. 

Cause  of  Death  :     Pernicious  anemia. 

Necropsy  Protocol. — Xecropsy  was  performed  ten  hours  after  death.  K.xternal 
Examination:  The  body  is  that  of  a  slenderly  built,  poorly  nourished,  white  male 
child,  nine  years  of  age.  The  skin  has  a  bluish  gray  appearance  over  the  abdomen  and 
lower  chest,  with  yellowish  cast  of  all  muscle  depressions  over  the  chest  and  neck. 
There  is  a  faint  yellowish  tinge  to  the  sclerae.  The  submaxillary  glands  are  promi- 
nent. The  lymph  modes  posterior  to  the  sternocleidomastoid  as  well  as  the  axillary 
and  inguinal  glands  are  palpable.  The  pupils  are  unequal,  the  right  being  2  mm.  and 
the  left  4  mm.  in  diameter.  The  teeth  are  also  unequal  in  size.  Rigor  mortis  is  pre=  - 
ent.    The  body  length  is  127  cm. 


i 

! 

^^tf^ 

f 

1 

Fig.  17  (Case  3).  Section  of  the  dorsal  region  of  the  spinal  cord.  The  right 
lateral  column  is  principally  involved.  Some  degeneration  changes  have  also  occurred 
in  the  anterior  columns.     (XIO.') 


Ventral  Section:  The  fat  over  the  abdomen  is  of  a  pale  lemon  color  and  moist. 
The  muscles  are  red.  The  lower  border  of  the  liver  is  5  cm.  below  the  ensiform  carti- 
lage. It  is  brown  in  color.  The  spleen  is  large  and  free.  The  appendix  is  also  free 
and  measures  8  cm.  in  length.  The  mesenteric  lymph  nodes  are  enlarged  and  some 
are  calcareous.  The  diaphragm  arches  to  the  third  interspace  on  the  right  and  to  the 
fourth  interspace  on  the  left. 

Heart:  The  heart  muscle  is  firm,  grayish  pink  in  color  and  shows  no  white  areas 
or  fat. 

Lungs:  Both  lungs  showed  slight  congestion  in  the  posterior  portions  of  the  lowei 
lobes. 

Organs  of  the  Xeck :  The  thymus  is  present.  The  tissue  is  stringy,  but  very  little 
of  the  gland  tissue  is  left. 

Abdomen:  The  spleen  shows  three  fetal  lobulations.  The  pulp  is  firm  and  the 
nialpighian  bodies  numerous.  The  kidneys  show  nothing  abnormal.  The  liver  weighs 
1,240  gm.,  and  a  cut  section  looks  greenish  yellow.  It  is  homogeneous,  there  being  very 
scant  outlining  of  the  lobules. 

Gastro-Intestinal :  There  were  depressions  in  the  gastric  mucosae  suggesting  begin- 
ning ulcerations. 

Head:  The  .skull  is  pale  in  color  and  shows  irregular  thinning  over  the  vortex  and 
frontal  region. 

Brain :  The  dura  is  adherent  to  the  calvarium.  The  cortex  shines  through  a  thin 
and  delicate  pia  mater  which  is  gray.     The  cranial  nerves  appear  smaller  than  usual. 

Pane  .108 


LOUIS  A.  LURIE 


The  frontal  lobes  appear  out  of  proportion  to  the  parietal.  The  temporal  tips  are  un- 
equal in  pattern,  the  left  being  more  complex  than  the  right.  The  hemispheres  of  the 
cerebellum  are  also  slightly  unequal,  the  left  being  the  larger.  The  brain  substance  is 
firm,  especially  the  right  frontal  region.  The  weight  of  the  brain  is  1,280  gm.,  which 
represents  a  gain  of  264  gm.,  according  to  Tigges'  formula. 

Cord :  The  cord  shows  "china  white"  softening  in  the  posterior  columns,  espe- 
cially in  the  lumbar  region. 

Histological  Examination. — Weigert  Sections — Left  Motor  Area:  In  the  sub- 
cortical areas,  the  perivascular  lymph  spaces  are  distended  and  clear.  Many  small 
discrete  foci  of  degeneration  and  four  larger  sclerotic  plaques  were  noted.  The  cortex 
itself  does  not  present  anything  unusual. 

Pons:  This  section,  like  the  two  preceding  sections  of  the  pons,  also  contain  the 
miliary  foci  of  Preobrajensky.  However,  they  are  not  nearly  as  numerous  nor  as 
universally  distributed,  being  limited  to  a  small  portion  of  the  medullary  substance. 
The  blood  vessels  in  the  nuclear  masses  are  thickened  and  filled  with  red  blood  cells. 
The  perivascular  spaces  are  markedly  di«;tfndcd,  and  sume  aU.)  c.intain  red  blood 
corpuscles. 


Fig  18  (Case  3)      lust  as  m  the  tuo  preciduig  ca; 
shows  the  miliary  foci  of  Preobrajensky      W  eigert's 


■s,  this  section  of  the  pr 
velin  sheath  stain. 


Medulla :  Here  there  is  only  slight  evidence  of  pathological  involvement.  The 
lesions  found  are  similar  to  those  described  above. 

Cord  :  (Scrvical  region.) — In  the  lateral  column,  near  the  anterior  horn,  there 
is  a  well-defined  focus  of  degeneration  of  the  Lichtheim  type.  The  lateral  cerebellar 
tracts  show  patchy  myelin  sheath  degeneration,  with  here  and  there  evidence  of  vacu- 
olization. (Dorsal  region.)— Here  the  lesions  are  even  more  marked.  The  antero- 
lateral columns  show  great  involvement.  Many  foci  of  degeneration,  including  a 
Lichtheim  focus,  are  seen.  The  blood  vessels  do  not  show  any  abnormalities.  (Lumbar 
region.) — This  section  shows  nothing  of  note. 

Cresylecht-Violet  Sections— Left  Motor  /Jrco.— The  principal  abnormality  noted 
was  on  the  part  of  the  pyramidal  cells.  A  large  number  of  these  cells  were  shrunken 
and  the  contour  of  their  nuclei  was  not  clear  cut.  Some  were  highly  granular  and 
some  were  surrounded  by  satellite  cells.  Here  and  there  in  the  subcortical  area  there 
were  small  vacuoles. 

Pons:  Here  the  changes  in  the  nerve  cells  are  similar  to  those  just  described,  only 
much  more  accentuated.  The  axonal  type  of  degeneration  was  observed.  The  larger 
pyramidal  cells  did  not  appear  to  be  as  greatly  involved  as  the  smaller. 

Page  .Wfl 


RAN  soil  OFF  MEMORIAL  VOLUME 


Medulla:  Here  one  notices  large  sclerotic  areas  which  are  apparently  closely  iden- 
tified with  the  blood  vessels.  Small,  clear,  hyaline-like  areas  are  fairly  numerous. 
The  nerve  cells  show  but  insignificant  changes. 

Cord:  (^Cervical  region.) — The  blood  vessels  are  slightly  thickened  and  the  peri- 
vascular spaces  are  distended  and  filled  with  hyaline-like  material.  (Dorsal  region.)  — 
Here  we  meet  with  ballooning  of  the  nerve  fibers  with  the  formation  of  clear  sieve-like 
spaces.  There  does  not  appear  to  be  an  increase  in  the  neuroglia.  Many  of  these 
irregular  areas  are  in  close  proximity  and  even  surround  tlie  blood  vessels.  The  cells 
in  the  anterior  horns  show  a  high  degree  of  chromatolysis.  Some  of  the  cells  appear 
to  be  entirely  disintegrated.  {Lumbar  region.) — In  this  region  there  is  very  little  of  a 
pathological  nature  to  be  seen. 

Case  4. — Necropsy  16-52. — History.) — J.  F.,  aged  53,  was  committed  to  the  North- 
ampton State  Hospital  for  the  Insane,  May  10,  1915.  The  medical  certificate  reads  as 
follows :  "Patient  is  recovering  from  an  acute  exacerbation  of  a  chronic  nephritis. 
Patient  has  a  cross  on  his  arm,  which  he  hopes  will  prove  certain  things  if  he  can  see 


Fig  19  (Case  4)  — Numerous  areas  of  degeneration  of  varying  sizes  are  shown  in 
this  picture  of  the  cortex  In  several,  the  close  relationship  to  the  blood  vessels  is 
seen.     \\  cigcrt's  myelin  slicath  stain. 


the  priest.  Wishes  to  see  the  selectmen  about  certain  property  and  wishes  to  tell  them 
that  while  there  is  life  there  is  hope ;  that  the  sky  is  blue  and  other  such  things. 
Wishes  to  see  a  lawyer  about  disposing  of  his  property.  Is  an  inmate  of  almshouse 
and  has  none." 

General  Af-pcarance. — The  patient  is  a  well-nourished,  simple  looking  man,  over 
50  years  of  age,  very  anemic  in  appearance.  During  the  examination  he  was  quiet, 
but  listless  and  indifferent.  He  did  not  volunteer  conversation,  replying  correctly, 
however,  when  directly  questioned.  There  was  no  stereotypy,  autonomy,  blocking  or 
flight  of  ideas,  or  other  abnormalities  noticeable,  except  possibly  a  slight  retardation. 
This  may  be  his  normal  reaction,  as  he  does  not  appear  overbright. 

Family  History. — His  father  is  said  to  have  been  insane.  One  brother  is  in  Bald- 
winville  (hospital  for  chronic  infantile  neurological  cases),  and  another  brother  was 

Page  SIO 


LOUIS  A.  LURIE 


in  the  Northampton  State  Hospital,  the  diagnosis  in  his  case  being  manic  depressive 
insanity. 

Personal  History.— The  patient  was  born  and  brought  up  in  Ware,  Mass.,  where 
he  spent  all  of  his  fife  except  for  short  occasional  absences.  He  can  only  read  and 
write.  He  was  never  employed  except  as  a  common  laborer.  He  worked,  however, 
only  intermittently,  and  for  the  greater  part  of  his  life  was  looked  after  by  his  sister. 
l'"or  the  past  several  years  he  has  been  in  poor  physical  health.  He  can  not  state  any- 
thing exact  concerning  this,  but  says  that  his  appetite  has  been  poor  and  that  he  believes 
he  has  kidney  trouble.  At  one  time  he  is  said  to  have  been  very  intemperate,  but  denies 
drinking  to  any  extent  for  several  years  prior  to  his  admission  to  the  hospital.     In  1910, 


Fig  20  (.Case  4)  — Weigcrt  section  of  the  puns.  In  this  photograph,  the  Lichtheim 
type  of  focus  predominates.  A  few  of  the  miliary  foci  of  Preobrajensky  are  also 
present     Note  the  distention  of  the  perivascular  spaces. 


he  was  committed  to  the  Howard  (R.  I.)  State  Hospital.  The  diagnosis  at  that  time 
was  delirium  tremens.  Three  years  later  he  was  again  admitted  to  the  Howard  State 
Hospital,  where  a  provisional  diagnosis  of  chronic  alcoholism  was  made.  The  mental 
examination  at  that  time  showed  depression  and  defective  knowledge  of  current  events. 
The  patient  denied  hallucinations,  but  it  was  stated  that  a  short  time  before  coming  to 
the  hospital  he  heard  noises  on  waking  from  sleep.  He  was  discharged  in  1914  and 
returned  to  his  home  from  where  he  was  sent  to  the  Ware  .Almshouse.  From  there 
he  was  committed  to  the  Northampton  State  Hospital. 

Physical  Examination. — A  summary  of  the  physical  examination  reads  as  follows: 
"Fairly  well  nourished  male  with  rather  poor  muscular  development  and  of  decidedly 

Page  Sit 


RANSOM  OFF  MEMORIAL  VOLUME 


anemic  appearance.  The  mucous  membranes  are  very  pale.  Tliere  is  a  complaint  of 
dyspnea  on  exertion  and  of  discomfort  after  eating.  Appears  very  much  like  per- 
nicious anemia." 

Neurological  Examination. — There  are  no  unusual  phenomena  observed.  The 
patient  is  quiet  on  examination.  .'\11  motions  are  slow  and  deliberate.  There  is  no 
tremor  or  flush. 

Muscle  Power:   This  is  poor. 

Co-ordination :  There  is  a  slight  swaying  in  the  Romberg  position,  but  he  is  able 
to  stand  without  support.  The  gait  is  normal.  Co-ordination  tests  were  fairly  well, 
although  slowly  performed. 

Sensation:  The  feet  and  hands  are  slightly  cooler  than  the  other  portions  of  the 
body.     Stereognostic  sense  is  normal. 

Cranial  Nerves :  The  pupils  are  normal  in  size  and  equal  and  react  to  light  and 
accommodation  .  All  the  other  cranial  nerves  are  normal. 

Reflexes:  The  superficial  reflexes  are  entirely  absent.  The  knee  jerks  are  absent. 
The  other   tendon   reflexes  are  verv   faint.     There  are  no  abnormal   reflexes. 


Fig.  21  (Case  4). — Section  of  the  cervical  region  of  the  spinal  cord.  The  pos- 
terior and  postero-lateral  columns  are  involved.  .A  narrow  strip  on  either  side  of  the 
posterior  fissure  has  escaped  involvement  in  the  pathologic  iirocess.  \\  eigert's  myelin 
sheath  stain.     (X  10.) 


Mental  Examination.— Or\cnta.Uon:  Good  in  all  spheres.  Memory:  Remote  and 
recent  memory  rather  poor.  He  remembers  things  in  general  ways  but  can  not  give 
details  nor  dates,  and  appears  somewhat  demented. 

Education :  He  is  very  poorly  educated.  He  can  read  and  write,  but  has  little 
general  knowledge,  and  no  knowledge  at  all  of  current  events. 

Delusions:  On  admission,  he  talked  of  vague  unsystematized,  indefinite  delusions 
of  owning  considerable  property  which  was  due  him  from  his  father's  estate.  Mild 
delusions  of  persecution  against  his  sister  were  also  present,  he  believing  that  she  had 
deprived  him  of  his  share  of  the  estate.  He  made  other  vague  statements,  but  his 
whole  delusional  formation  was  very  loosely  connected.  He  talked  only  when  directly 
questioned  and  gave  the  impression  of  being  considerably  deteriorated. 

Hallucinations :  No  definite  hallucinations  could  be  elicited.  The  abstract  from 
the  hospital  at  Howard,  R.  I.,  states  that  before  his  admission  there  he  was  hearing 
noises  on  waking  from  sleep.  This  may  possibly  have  been  a  mild  hallucinosis  follow- 
ing drink. 

Emotional  Tone:  He  takes  very  little  interest  in  anything  about  him.  He  shows 
neither  exhilaration  nor  depression,  but  always  appears  indifferent. 

Page  312 


LOUIS  A.  LURIE 


Demeanor:  Since  liis  admission  he  has  heen  quiet  and  fairly  cheerful.  He  never 
volunteers  conversation   with   anyone   but   answers   when   directly   questioned. 

Attention :    This  is  fair. 

Abstract  of  Ward  Notes. — On  admission,  he  was  correctly  oriented.  He  remem- 
hered  that  his  brother  had  once  lieen  a  patient  at  the  hospital.  The  patient  complained 
of  not  feeling  well  physically.  He  believed  he  had  kidney  trouble.  He  talked  vaguely 
of  his  delusions  and  denied  that  he  had  been  intemperate  in  recent  years.  He  was 
quiet  and  conducted  himself  well.     At  first  he  helped  a  little  in  the   ward   when   re- 


—■<■■■■- -:l:y. 


«:     *« 


VC^'^--  ■ 


•:;  -^ 


^1 


Fig.  22  (Case  4). — This  is  a  section  of  the  cortex  stained  with  cresylecht-violet. 
A  large  pyramidal  cell  (neuronophage)  can  be  seen  which  is  evidently  greatly  swollen 
and  undergoing  degeneration.  It  contains  two  glia  cells,  one  being  within  the  cell 
body  and  the  other  within  the  nucleus  in  close  contact  with  the  nucleolus.      (X  100.) 

quested,  but  made  no  attempt  to  associate  with  anyone,  although  he  could  not  be  con- 
sidered .surly.  When  addressed,  he  would  reply  but  would  not  continue  the  conversa- 
tion. He  took  no  interest  in  games,  in  reading  or  in  the  discussion  of  his  fellow- 
patients.  Whether  this  listlessness  was  due  to  deterioration  or  to  his  poor  physical 
condition  was  difficult  to  determine. 

In  June,  1915,  he  began  to  complain  of  epigastric  pain  and  of  a  feeling  of  heavi- 
ness following  the  taking  of  food.  In  September,  a  slight  dyspnea  was  noticed  on 
exertion  and  the  epigastric  distress  had  become  so  marked  that  he  could  only  take 

Page  SIS 


RANSOHOFF  MEMORIAL  VOLUME 


malted  milk,  vomiting  every  other  food.  The  skin  showed  the  peculiar  brown  tinge 
peculiar  to  pernicious  anemia.  A  single  blood  count  showed  3,260,000  red  blood  cells 
and  a  hemoglobin  of  60  per  cent.  Numerous  poikilocytes,  microytes,  and  macrocytes 
were  seen,  but  no  nucleated  reds  were  seen  at  this  time.  There  was  puffiness  about  the 
eyes.     Some  days  he  complained  of  weakness  in  the  legs. 

In  October,  physical  failure  became  more  marked.  The  dyspnea  was  so  intense 
that  care  in  bed  became  necessary.  Puffiness  of  the  eyes,  hands,  and  feet  was  very 
noticeable.  Mentally  he  was  very  dull,  apparently  comprehending  but  little.  In  No- 
vember, 1915,  a  note  in  tlie  history  was  maiU-  that  ho  seemed  slightly  improved,  which 
temporary   impro\emeiit   r.  .iiimiu  .1    luin;        ;    :,    i''.'-       In    Jaiuiar>-,    l''i(i,    iiiiioal    liiid- 


Fig.  23  (Case  4).- — .Another  view  of  the  cortical  motor  area  showing  disintegration 
of  the  pyramidal  cells,  and  distention  of  the  pericellular  spaces.  Some  of  these  cells 
are  pale,  shrunken,  irregular  in  outline,  stain  poorly  and  unevenly,  and  show  eccen- 
tricity of  the  nucleus.  The  severe  neurogliar  reaction  is  evident.  In  the  lower  right 
hand  corner  of  the  field,  note  the  large  sclerotic  area  surrounding  a  blood  vessel. 
Cresylecht-violet  stain.     (  X  50. ) 

ings  of  pernicious  anemia  were  present  in  the  blood  and  especially  the  nucleated  red 
blood  cells.  Early  in  April  he  failed  rapidly  and  died  on  .April  15,  without  showing 
any  new  development  of  his  disease. 

Necropsy. — Protocol  (16-52). ^Necropsy  was  performed  two  hours  after  death. 
The  body  is  that  of  a  white  male,  168  cm.  in  length.  The  skin  is  pale  lemon  yellow, 
especially  over  cheeks,  forehead,  and  arms  and  legs.  There  is  considerable  pigmenta- 
tion over  the  back,  chest,  face  and  lower  abdomen.  Rigor  mortis  is  present  in  jaws 
and  legs.  The  lymph  nodes  are  not  palpable.  The  pupils  are  equal  and  measure  0.4 
cm.  in  diameter.     The  eyeballs  are  slightly  softened.     The  teeth  show  Riggs'  disease. 

Ventral  Section :  The  fat  over  the  abdomen  is  pale  yellow  and  moist.  The  muscles 
are  red  and  mixed  with  apparent  fatty  streaks.  The  lovver  border  of  the  liver  is  1  cm. 
below  the  ensiform  cartilage.  There  is  a  slight  amount  of  free  fluid  in  the  flanks. 
The  appendix  is  8  cm.  in  length.  The  tissue  in  the  pelvis  appears  bloodless.  The 
spleen  is  surrounded  by  adhesions.     The  diaphragm  arches  to  the  third  rib. 

Thorax:  The  sternal  marrow  is  richly  red  and  somewhat  fluid.  There  is  a  free 
fluid  in  the  left  chest  and  the  pericardial  sac  is  thickened. 

Page  Sli 


LOUIS  A.  LURIE 


Heart :  The  epicardial  fat  is  abundant  and  there  are  milk  spots  on  the  posterior 
surface.  The  heart  muscle  shows  white  mottling  and  also  minute  hemorrhages  in  the 
right  auricle.     It  fragments  easily. 

Lungs :    They  show  very  little  of  note. 

Abdomen:  The  spleen  is  grayish  red  and  its  capsule  is  slightly  withered.  A  sec- 
tion shows  the  pulp  to  be  red.     It  measures  10  by  5  by  2  cm. 

.\drenals :   These  are  small  and  softened. 

Kidneys:  There  is  an  excessive  amount  of  fat  around  the  kidneys  which  are 
yellowish  brown  in  color.  The  pyramids  are  white  and  poorly  differentiated  from  the 
surrounding  tissue.     Two  cysts  containing  fluid  are  seen. 

Liver :  There  are  slight  irregularities  over  the  surface  of  the  liver  which  is  yel- 
lowish red  in  color.  ,\  section  shows  packing  together  of  the  lobules.  It  measures 
23  by  16  by  7  cm. 

Pancreas :    This  organ  is  dotted  with  hemorrhages. 

Gastro-Intestinal :  The  stomach  is  large  and  contains  some  fluid.  The  mucous 
membrane  of  the  stomach  is  shiny. 

Brain:  The  dura  shows  signs  of  absorption  in  the  frontal  region  and  of  thicken- 
ing along  the  longitudinal  sinus.  A  slight  amount  of  yellow  fluid  escapes  on  section 
of  the  dura.  Points  of  hemorrhages  are  seen  in  the  pia  mater  which  shows  some 
thickening  along  the  vessels.  It  is  held  up  from  the  cortex  by  fluid  in  the  motor 
regions.  The  brain  appears  \ellr>\vish  white.  The  right  lobe  sags,  being  apparently 
slightly  shorter  than  the  left.  The  pattern  of  convolutions  is  more  nearly  circular 
over  the  right  lobe  than  over  the  left  lobe.  The  brain  has  a  resilient  feeling.  From 
the  basal  aspect,  it  is  noticed  that  the  pia  is  thickened  over  the  pons,  left  third  nerve, 
and  optic  chiasm.  The  left  temporal  tip  is  softer  than  the  right.  The  left  cerebral 
artery  is  larger  than  the  right.     The  fourth  ventricle  is  clear. 


Colloidal  Gold  Reaction 


1I2!3|415|6|718|9J_10 

Right    base .0  0  0  1  i'l  H»  OlOlO 

Left  base ^ ....  .^  ..........  .(mmi  n  i  u  mHO 

Third    ventricle* I M  i  (MilMl  DiKVO 

Spinal   fluid Oil  (MHIOU  0  0|0 

Pericardial    fluid ..  .^^.  .  .  .0  i»'(Hi(HMro'0'0 

*  Slightly  bloody. 

Histological  Examination. — U'ciycrl  Scstion — Left  Motor  Area. — The  medullarv 
substance  shows  little  of  note.  Ther  are  a  few  areas  where  the  myelin  has  been  com- 
pletely destroyed  and  also  a  few  places  where  there  is  a  thinning  out  of  the  myelin. 

Paralleling  the  edge  of  the  cortex,  there  is  a  narrow  strip  of  tissue  which  stains 
less  heavily  than  the  surrounding  tissue.  Under  high  power,  this  area  is  shown  to 
contain  small  irregular  shaped  spaces  which  for  the  most  part  are  structureless.  A 
few  are  crossed  by  undegenerated  or  only  partially  degenerated  nerve  fibers.  In  this 
area,  furthermore,  the  capillaries  are  very  numerous  and  the  perivascular  spaces  are 
distended. 

Pons :  Here  we  see  large  foci  of  destroyed  tissue  in  intimate  relation  with  the 
blood  vessels.  It  is  almost  possible  to  trace  the  entire  process  of  their  formation  as 
they  are  present  in  all  .stages  of  development.  One  notices  first,  a  sliglit  thinning  out 
of  the  myelin  sheaths  in  the  immediate  neighborhood  of  a  blood  vessel.  The  process 
continues  and  this  thinnned  out  area  becomes  sievelike,  due  to  the  lack  of  uniformity 
in  the  destruction  of  the  myelin  sheaths.  In  the  meshes  of  some  of  these  cribriform 
areas,  red  blood  cells  are  found.  In  the  more  advanced  places,  there  has  been  an 
increase  in  the  neuroglia  with  resultant  formation  of  large  plaques  of  sclerotic  tissue. 
In  one  part  of  the  field,  the  miliary  foci  described  by  Preobrajensky  were  also  ob- 
served. 

Medulla:  Small  ragged  foci  of  destroyed  tissue,  irregularly  distributed  are  seen. 
The  perivascular  spaces  of  the  blood  vessels  in  the  olivary  nuclei  are  markedly  dis- 
tended. 

Cord:  (Cervical  region.)— In  this  region,  there  are  numerous  small  foci  where 
the  myelin  sheaths  have  been  destroyed  with  subsequent  vacuolization.  This  destruc- 
tive process  has  occurred  principally  in  the  columns  of  Burdach.  The  columns  of  Goll 
are  but  slightly  affected.    The  direct  pyramidal  tracts  show  more  or  less  degenerative 

Page  SIS 


RANSOM  OFF  MEMORIAL  VOLUME 


changes  also.  (Dorsal  region.) — This  region  appears  practically  normal.  In  the  gray 
matter  of  the  anterior  horns  one  can  see  several  small  hemorrhagic  areas.  This  is 
also  present  in  the  lumbar  region  which  otherwise  shows  nothing  of  note. 

Cresylccht-Violet  Sections. — Left  Motor  Area. — The  cortical  region  shows  exten- 
sive pathologic  involvement.  There  is  a  tremendous  overgrowth  of  neviroglia  both  of 
the  libers  and  cells.     The  latter  are  encroaching  on  the  pyramidal  cells.     The  glia  cells 


I'ig.  24  (Case  1  ). — Sectien  I'f  cirvical  region  of  spinal  cord  stained  with  cresylecht- 
violct  sliowing  sdihc  antcrinr  h.irn  cells  containing  yellow  pigment.  This  pigment  is 
diffuse,  slightly  granular,  and  occupies  the  central  portion  of  the  cell  body,  the  proto- 
plasmic substance  being  pushed  to  the  extreme  periphery.  The  two  cells  in  the  lower 
left  hand  corner  of  the  field  are  practically  nothing  but  a  mass  of  pigment.     (X  100.) 


are  of  two  kinds:  (1)  a  small  and  apparently  homogeneous  cell,  and  (2)  a  large  cell 
with  a  granular  nucleus  which  in  many  ways  resembles  a  small  lymphocyte.  In  sev- 
eral instances  these  cells,  both  large  and  small,  are  seen  to  be  incorporated  in  the  body 
of  the  pyramidal  cells,  and  in  one  instance  one  of  these  larger  cells  is  seen  to  be  in- 
corporated within  the  nucleus  of  the  nerve  cell.  The  nerve  cells,  with  but  few  excep- 
tions, show  marked  degenerative  changes.  They  are  shrunken,  irregular  in  outline, 
and  the  protoplasm  is  not  uniform  in  structure.  The  nuclei  show  chromatolysis  and 
their  outline  is  hazy.  Their  position  varies,  being  either  to  one  side  or  at  the  end  of 
the  cell.  Some  of  the  cells  instead  of  being  shrunken  are  tremendously  swollen.  In 
some  cases,  the  nerve  cell  seems  to  have  disappeared  entirely  or  fallen  out,  tl#  peri- 
cellular spaces  being  occupied  by  glia  cells. 

The  blood  vessels  also  show  a  severe  reaction.     The  perivascular  spaces  are  dis- 
tended.    The  capillaries  show  a  tremendous  increase.     One  sees  them  in  all  stages  of 

Page  S16 


LOUIS  A.  LURIE 


development,  from  the  small,  budding,  rod-like  projection  to  the  thin-walled  vessel 
with  an  almost  imperceptible  lumen. 

.'Ml  tlicse  pathologic  changes  gradually  decrease  in  intensity  as  we  approach  the 
subcortical  area.  In  the  latter  structure,  there  are  many  clear  areas  in  which  no  nerve 
libers  are  seen.  These  areas  are  irregular  in  size  and  shape.  In  the  larger  ones,  glia 
fibers  have  replaced  the  nerve  fibers,  giving  the  area  a  hyaline-like  appearance.  This 
is  brought  out  very  distinctly  with  the  eosinmethylene  blue  stain. 

Right  Peduncle:  There  is  a  uniform  distention  of  the  perivascular  spaces,  many 
of  which  are  contiguous  to  foci  of  degeneration.  Some  of  htese  areas  are  cribriform 
or  sievelikc  in  appearance.  The  pyramidal  cells  show  evidence  of  involvement.  Some 
are  completely  disintegrated,  some  have  lost  their  nuclei  and  are  highly  granular,  and 
others  are  pigmented.     Satellitosis  is  marked. 

Pons:  Small,  clear,  fairly  regular  areas  corresponding,  in  all  probability,  to  the 
miliary  foci  of  Preobrajensky  that  were  seen  in  the  Weigert  Section,  are  present  in 
the  raphe.  The  nerve  cells  do  not  show  as  great  an  involvement  as  those  in  the  pre- 
ceding sections.  Only  a  comparative  few  are  entirely  disintegrated  and  none  show 
pigmentation.  The  perivascular  spaces  are  distended.  There  are  also  patches  of 
neuroglia  overgrowth. 

Medulla:  The  nerve  cells  in  the  different  collections  of  gray  matter  show  uni- 
form degeneration  of  varying  intensity.  The  pcricrlhilar  spaces  are  enlarged.  Pig- 
mentation occurs  frequently.  Some  of  the  blond  mss.K  show  a  thickening  of  the 
intima  and  a  small  number  are  surrounded  by  small  .irras  ni   degeneration. 

Cord:  (Ccrru-ul  r,;,i. ni)  -Thvrr  \<  :i  sharply  dclined  sclerotic  area  In  llie  pos- 
terior column  wliirli  is  iilnitical  Willi  llial  seen  in  the  Weigert  Sccln.n.  Tins  area  is 
composed  cliiell\"  nf  massnc  \va\  >■  luindlrs  ..f  lu-uroglia  fibers  with  which  are  inter- 
mingled an  iiccasi.iiial  undegeneralcd  nr  .inlx  [lartially  degenerated  iur\  c  (ibril.  The 
nerve  cells  in  the  posterior  horn  appear  shrunken  in  size  and  the  nuclei  do  not 
stain  well.  The  anterior  horn  cells  show  some  pigmentation.  This  is  especially 
of  which  are  contiguous  to  foci  of  degeneration.  Some  of  these  areas  are  cribriform 
true  of  those  in  the  lumbar  region.  The  character  and  location  of  this  pigment  arc 
different  from  tli.it  of  the  pigment  normally  present  in  the  cells  of  people  fifty  years 
or  older.  In  this  case,  the  pigment  is  granular,  and  diffusely  and  evenly  distributed 
ever  the  central  portion  of  the  cell. 

DISCUSSTOX 

A  brief  resume,  contrasting  the  clinical  with  the  ]xilhologic  findings 
reveals  a  fairly  uniform  and  definite  relationship.  In  Case  1,  we  can  assume 
from  the  history  that  the  condition  had  probably  existed  for  about  three 
years  although  a  blood  examination  was  made  only  five  days  before  death. 
On  the  clinical  side  we  find  a  typical  blood  picture  of  pernicious  anemia; 
absence  of  all  the  superficial  reflexes  with  the  exception  of  the  left  inguinal 
reflex  ;  absence  of  both  patellar  reflexes  and  sensory  disturbances  in  the  form 
of  numbness  of  the  feet.  Mentally,  the  patient  had  visual  hallucination.s, 
paranoid  ideas  and  mild  delusions  of  persecution.  The  necrop.sy  report 
showed  the  characteristic  changes  on  the  part  of  the  heart  and  stomach. 
Contrasted  to  this  clinical  picture  there  are  definite  pathologic  findings.  In 
the  motor  area  we  find  characteristic  vascular  changes,  pyramidal  cell 
changes,  satellitosis,  vacuolization  and  the  presence  of  the  Lichtheim  foci 
of  degeneration.  In  the  pons  we  have  in  addition  to  the  above  changes  the 
miliary  foci  of  Preobrajensky.  In  the  spinal  cord,  the  posterior  column  is 
practically  entirely  destroyed,  especially  in  the  cervical  region.  Neural  and 
vascular  changes  are  also  present.  Pigmentalion  of  the  cells  is  pronounced 
and  the  neuroglia  changes  marked. 

In  Case  2  there  is  a  definite  bloml  ijiclure  of  pernicious  anemia.  From 
the  history  we  can  safely  infer  that  the  condition  had  existed  for  many  years. 

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RANSOM  OFF  MEMORIAL  VOLUME 


Clinically,  there  are  neurlogical  disturbances  in  the  form  of  hyperesthesia 
of  the  lower  extremities  and  an  unsteady  gait  and  mental  symptoms  simi- 
lar to  Case  1,  namely:  visual  hallucinations,  delusions  of  persecution,  and 
paranoid  ideas.  The  necropsy  examination  revealed  a  pale,  glassy  atrophic 
stomach  and  a  heart  with  tiger-lily  striations.  Histologically,  the  cortex 
showed  areas  of  degeneration  with  vacuole  formation,  vascular  changes, 
pyramidal  cell  changes,  satellitosis  and  a  marked  increase  in  the  neurogliar 
elements.  The  pathology  of  the  pons  was  practically  the  same  as  that  of  the 
cortex,  but  again  with  the  addition  of  the  miliary  foci  of  Proebrajensky. 
The  spinal  cord  presented  practically  the  same  pathologic  picture  as  the 
first  case. 

In  Case  3  the  clinical  picture  is  somewhat  different.  In  the  first  place 
the  patient  was  very  young,  being  about  nine  years  old  at  the  time  of  his 
death ;  in  the  second  place  he  was  a  decided  epileptic,  and  in  the  third  place 
the  onset  of  the  pernicious  anemia  was  acute.  Hence,  clinically,  we  have 
comparatively  few  findings.  There  were  no  neurological  changes,  but  men- 
tally he  showed  delusions  of  persecution  and  paranoid  ideas.  During  the 
height  of  the  fatal  attack,  he  showed  a  marked  psychosis.  On  necropsy, 
there  were  slight  changes  in  the  stomach,  resembling  beginning  minute  ulcer- 
ations. The  heart  was  negative.  The  brain  showed  a  gain  in  weight,  accord- 
ing to  Tigges'  formula,  of  264  gm.  However,  Tigges'  formula  is  not 
strictly  applicable  to  children.  Pathologically,  in  the  cortex,  the  changes 
were  similar  to  those  in  the  first  case  except  that  they  were  less  marked.  No 
neurogliar  changes  were  seen,  which  was  to  be  expected,  considering  the 
short  duration  of  the  disease.  On  the  whole,  the  changes  in  this  case  wen- 
the  least  marked.  Here  again,  however,  the  miliary  foci  of  Preobrajensky 
were  found  in  the  pons. 

In  Case  4  the  process  evidently  had  gone  on  for  several  years.  The  blood 
picture  was  typical.  There  were  marked  neurological  disturbances,  all  the 
superficial  reflexes  and  both  knee  jerks  being  absent.  There  was  also  a 
distinct  weakness  of  the  legs.  Mentally,  there  were  paranoid  ideas  and  delu- 
sions of  persecution  and  other  vague  unsystematized  delusions.  No  definite 
hallucinations  were  elicited.  On  necropsy  the  heart  showed  milk  spots, 
white  mottling,  and  minute  hemorrhages.  The  mucous  membrane  of  the 
stomach  was  shiny.  The  histopathologic  changes  were  similar  to  those  in 
Case  2.  No  Lichtheim  focus  was  seen  in  the  cortex.  There  was  a  marked 
increase  in  the  neurogliar  elements.  Neuronophagic  actions  of  the  cells  was 
marked.  The  pons  showed  the  milary  foci  of  Preobrajensky,  the  Lichtheim 
foci,  vascular  changes  and  slight  nerve  cell  changes.  In  the  spinal  cord,  the 
columns  of  Burdach  showed  the  greatest  involvement.  The  nerve  cell 
changes  were  slight.  Pigmentation  was  present.  Also  vascular  changes. 
There  was  a  considerable  increase  in  the  neuroglia. 

Page  S18 


LOUIS  A.  LURIE 


The  following  tables  show  these  results  in  tabular  form : 

TABLE  1.— SuMMAKY  on  Clinical  Findings  in  the  Cases  Reported 


I.   Duration: 

(a)    From  symptomatic  stand- 

Case    1 

Normal 
All    absent    ex- 
cept   left   in- 
Ruinal 

Numbness  of 
f.et 

i 

Irfmon    yellow 
Lemon    yellow 

Yel.   Pink 

Raspberry  red 

EnlarRed 

white   stria- 

165  Rrams 

1.800  Rrams 
Thick  walls: 
glossy:    no 

LossToS 

Minut'e^pecks 

of    translu- 
cency  in  pos- 
terior columns 

Case    2 
M,_rs 

N^o^sfe 

Hyperesthesia 
of   lower   ex- 
steady    Rait 

+ 
-1- 

-f 

Lemon  yellow 
Not    Riven 

TiRer  lily 

enlarRement 

185  Rrams 

1.560    Rrams 

Pale.  Rlossy. 

atrophic 

Loss  81 

NoTsuled 

Case    3 

^cul^ 

Normal 
Normal 

Normal 
None 
None 

None 

-4- 

Yellowish 

'^No'r-Ri^^'n" 

Normal 

160  Rrams 

1.240  Rrams 
Ulcerations? 

Cain  264 

China"w1ute 

softenine  in 

posterior 

columns 

Case   4 

(b)   lyaboratory     standpoint.. 

Several 

3.   NeuroloRic    Findinss: 
(a)  Pupils 

+ 

(b)    Superlicial     reflexes 

Normal 
Absent 

(d)  Abnormal    reflexes 

(e)  Sensory     disturbances... 

4.   Mental  FindiiiKs: 

(a)  Hallucinations     (visual). 

(b)  Delusions  of  persecution. 

Absent 

None 

Weakness  of 

leRs 

Doubtful 

-1- 

5.  Necropsy    FindiuRs: 

(a)    Skin            

(c)  Marrow:     (a)    Sternum.. 

(b)    Femur.... 

(d)  Heart 

Pale    yellow 
Richly  red 

No   enlarRe- 
ment. milk 
spots,    white 
mottlinR:  hem- 
orrhaRes 

13.5  X  10  X 

(e)    Stomach    

23  xl6x7  cm. 
Mucous   mem- 
brane  shiny 

(i)     Cord 

Not   Riven 

Not  stated 

TABLE  2. — SuMMAuv  or  Histologic  Findings  in  the  Sekies  of  Cases  Reported 


From  the  above  tables,  it  is  evident  that  the  neuropathology  of  the  brain 
in  pernicious  anemia  is  larger  and  more  fruitful  than  that  of  the  cord.  It  is 
true,  of  course,  that  all  these  cases  showed  very  definite  mental  symptoms 
and  hence  one  would  naturally  expect  to  find  cortical  changes.  However,  in 
the  case  of  J.  H.  (Case  3).  who  had  a  definite  psychosis  with  no  neurolog- 


RAX  so  J I  OFF  MEMORIAL  VOLUME 


ical  disturbances,  tlie  cord  changes  were  by  far  more  marked  and  bad  pro- 
gressed much  farther  than  the  cortical  changes.  From  this  one  might  argue 
that  in  pernicious  anemia,  the  first  degenerative  changes  occur  in  the  cord : 
then  the  process  gradually  extends  and  involves  the  brain. 

In  the  third  case,  there  was  also  very  little  involvement  of  the  neuroglia. 
This,  as  well  as  all  the  other  points  in  which  this  case  differed  from  the 
others,  can  be  readily  explained  on  the  ground  that  this  case  had  an  acute 
onset  and  ran  a  very  rapid  course. 

The  significance  of  the  presence  of  the  miliary  foci  of  Preobrajensky 
in  every  section  of  the  pons  is  open  to  speculation.  Are  these  lesions  spe- 
cific for  pernicious  anemia  or  is  their  uniform  presence  in  the  pons  merely 
a  coincidence?  Obviously,  one  should  not  generalize  from  the  findings  of 
only  four  cases.  However,  to  look  on  the  regularity  of  their  presence  at 
merely  a  coincidence  seems  to  me  to  be  unjustifiable.  At  any  rate,  it  is  a 
point  worthy  of  note  and  of  further  investigation. 

COXCI.USIOXS 

1.  There  appears  to  be  a  fairly  definite  and  constant  relationship  be- 
tween the  clinical  symptoms  and  the  pathologic  changes. 

2.  The  psychoses  can  be  classified  with  the  symptomatic  psychoses  of  a 
toxic-organic  nature.  The  whole  delusional  formation  is  vague,  unsystema- 
tized and  loosely  connected.* 

3.  The  brain  changes  are  even  more  marked  than  the  cord  changes  pro- 
vided the  disease  has  existed  for  a  considerable  length  of  time.  This,  in 
my  opinion,  is  due  to  the  fact  that  in  addition  to  the  toxic  action  of  the  poi- 
son on  the  pyramidal  cells,  metabolic  changes  also  occur  in  the  nerve  cells  as 
a  direct  result  of  the  long  standing  anemia. 

4.  The  blood  vessels,  pyramidal  cells  and  the  medullary  fiber  show  simi- 
lar degenerative  changes  at  different  levels  of  the  central  nervous  system. 

5.  The  foci  of  degeneration  bear  a  definite  and  distinct  relationship  to 
the  blood  vessels. 

6.  In  every  case,  the  miliary  foci  of  F'reobrajensky  were  found  in  the 
pons. 

7.  Some  of  the  nerve  cells  in  every  case  with  the  exception  of  the  third 
case,  which  was  of  very  short  duration,  show  dift'use  pigmentation. 

8.  In  speaking  of  the  neuropathology  of  pernicious  anemia,  it  is  not 
sufficient  merely  to  describe  the  lesions  found  in  the  spinal  cord.  The  brain 
changes  are  too  numerous  and  definite  to  be  omitted.  The  neuropathology  of 
pernicious  anemia  should  include  the  entire  central  nervous  system. 

I  wish  to  express  my  thanks  to  Dr.  Elmer  E.  Southard  not  only  for  placing  the 
clinical  material  at  my  disposal,  but  also  for  his  many  helpful  suggestions  m  carrying 
out  this  study.  1  also  wish  to  thank  Dr.  M.  M.  Canavan  for  her  kindly  interest  and 
capable  supervision.  These  have  been  of  inestimable  value  to  ine  in  the  preparation 
of  this  paper.  My  thanks  are  also  due  to  Miss  E.  R.  Scott  for  her  care  in  the  prepara- 
tion of  the  sections  and  to  Mr.  H.  VV.  Taylor  for  his  care  in  the  preparation  of  the 
photographs. 

*  It  is  quitt!  possible  that  fnrtlier  investigation  will  prove  that  these  psychoses  are  due  to  an 
encephalitis,  and  that  therefore  they  belong  in   the  ^roup  uf  encephalopsychoses   rather  than   in   the 


\ 

LOUIS  A.  LURIE 

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Kahn.  M.,  and  Barskv,  T.:  Studies  in  the  Chemistry  of  Pernicious  Anemia,  .\rch.  Int.  Med. 
23:334    (March).    1919. 

Langdon,  F.  W.:  Nervous  and  Mental  Manifestations  of  Pre-Pernicious  Anemia.  T.  A.  M.  A. 
45:11,35    (Xov.   25).    1905. 

Lichtlieini:     Zur   Kenntnis  der  pernici6sen   Anamie,  Verhandl.  d.  Cong.  f.   inn.   Med.  6:84,    1887. 

Marcus,  IL:    Psychose  bei  pernicioser  anamie,  Neurol.  Centralbl.  22:453,   1903. 

McCrae,  T.:  Pernicious  Anemia:  The  Statistics  of  a  Series  of  Forty  Cases,  J.  A.  M.  A.  28: 
I -IS    (June    18),    1902. 

Minnich.  W. :  Zur  Kenntniss  der  im  \'erlauf  der  perniciosen  .\namie  beobachteten  spinal  Fr- 
krankungen,    Ztschr.    f.    klin.    Med.    21:25    and    264,    1893;    ibid.    22:60.    1893. 

Moffit,  H.  C:  The  Function  of  the  Spleen  with  Particular  Reference  to  Haemolyses  and  the 
Hacmolytic  Anemias,  Bost.  M.  &  S.  J.   171:1639,   1914. 

Moffit,   H.    C:     Studies   in    Pernicious   Anemia,    Am.    J.    M.    Sc.    148:289.    1914. 

Nonne,  M.:  Weitere  Beitrage  Zur  Kenntniss  der  im  Verlaufe  letaler  Anamien  beobachteten 
Spinalerkrankungen,    Deutsch.   Ztschr.   f.   Nervenh.    6:313,    1894-1895. 

Nothnagel's    Encyclopedia   of   Practical    Medicine,    Am.    Ed.,    1909.    Diseases    of    the    Blood. 

Osier,   William,   and   McCrae,   Thomas:     Modern    Medicine,    1915. 

Patek,    A.   J.:     Family    Pernicious   Anemia.    J.    A.    M.    A.    56:1315    (May    6).    1911. 

Pearce.  R.  M.;  Krumbhaar,  E.  B.,  and  Frazier,  C.  H.:  The  Spleen  and  Anemia,  1918,  T.  B. 
l.ippincott  Co.,   Philadelphia. 

Pfeiffer.  I.  A.:  Neuropatholocical  Findings  in  Case  of  Pernicious  Anemia  with  Psychic  Impli- 
cation, J.   Nerv.  &  Ment.   Dis.  42:75,   1915. 

Preobrajensky,  P.  A.:  Die  Verandrungen  im  Nervensystem  in  einem  Fille  von  Anamia  Per- 
niciosa   Acuta,   Neurol.   Centralbl.,    1902,   p.   727. 

Putnam,  T.  J.,  and  Taylor,  E.  W. :  Diffused  Degeneration  of  the  Spinal  Cord,  I.  Nerv.  it 
Ment.    Dis.   28:1,    1901. 

Richter,   E.:     Ueber   Spinal  affektion  bei  letaler   Anemia,   Berl.  klin.   Wchnschr.  49:1976,    1912. 

.\.  W. :    Disturbances  of  the  Central  Nervous  System,  accompanying  Pernicious  Anemia. 

ungen  in  der  Ilirnrinde  bei  schwerer  .\namie.  Berl.  klin. 
wchnschr.    48:2357.    1911. 

Shaijiro:  Ilerlung  der  pernicioser  Anaemic  durch  abtreibung  von  Bothriocephalus  latus.  Ztschr. 
f.   klin.    Med.    13:1888. 

Strumpell,    A.:     A  Textbook  of   Medicine,   Vol.   2,    D.    Appleton   &   Co.,    New    York,    1912,   p.    58. 

Wiltschur:  Zur  Pathogenese  der  progressiven  perniciosen  Anamie.  Deutsch.  med.  Wchnschr.. 
1893. 

Woltman.  II.  W. :  Brain  Changes  Associated  with  Pernicious  Anemia,  Arch.  Int.  Med.  21: 
791    (June),   1918. 

Woltman,  II.  W. :  The  Nervous  System  in  Pernicious  Anemia:  .\n  .\nalvsis  of  One  Ilundied 
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THE  TUBERCULOSIS  PROBLEM  IN  CINCINNATI.* 

B.  F.  Lyle,  M.D., 

Cincinnati. 

PART  I. 

\\'hile  the  science  of  eugenics  is  engaging  popular  attention  and  the  re- 
sults of  the  activities  of  the  spirochetse  pallida  and  the  corpuscles  of  Neisser 
are  being  disclosed  to  the  public,  the  importance  of  the  universal  plague, 
tuberculosis,  can  not  be  obscured.  The  fact  that  the  mortality  from  this 
disease  in  Cincinnati  is  large,  and  its  relative  frequency  sufficiently  marked 
to  cause  comment  in  other  quarters,  has  been  recognized  by  the  profession 
and  the  public  in  general,  although  in  no  other  place  have  there  been  more 
energetic,  persevering  and  thorough  efforts  made  to  carry  out  those  meas- 
ures which  have  been  regarded  as  efficacious  in  stamping  out  the  contagion 
and  in  caring  for  its  victims.  The  fact  that  these  eiiforts  have  had  little  or 
no  effect  in  accomplishing  the  desired  end  makes  it  necessary  for  us  to  ascer- 
tain the  recent  discoveries  in  the  field  of  tuberculosis  in  order  that  we  may 
be  able  to  work  more  intelligentlj'  and  hopefully.  In  the  consideration  of 
the  subject  it  is  important  to  know  when  and  how  infection  occurs;  if  an 
individual  once  infected  becomes  immune  to  reinfection ;  what  influence 
early  infection  has  upon  the  subsequent  course  of  the  disease. 

Fortunately  the  clinical  manifestations  of  the  disease  do  not  give  an 
adequate  idea  of  the  extent  of  the  infection.  In  this  paper  an  attempt  will 
be  made  to  show  that  tuberculosis  is  almost  universally  disseminated  in 
civilized  countries  and  infection  occurs  early  in  life;  that  the  characteristics 
of  the  prevailing  lesions  and  consequent  variability  and  rapidity  of  progress 
depend  upon  heredity  and  the  degree  of  communal  infection;  that  the  mor- 
tality from  the  disease  is  largely  influenced  by  heredity,  sanitation  and 
climatic  conditions;  that  our  methods  of  prevention  are  faulty  in  conception 
and  lacking  in  results ;  that  while  there  is  a  possible  means  of  prevention, 
it  is  perhaps  impracticable,  makiiig  it  necessary  for  the  community  to  wait 
for  and  depend  upon  inherited  and  acquired  powers  of  resistance  and  im- 
proved sanitary  conditions  for  general  relief. 

As  research  work  in  this  city  and  country  is  not  sufficient  to  enable  us 
to  interpret  local  conditions,  I  have  not  hesitated  to  appropriate  any  ma- 
terial that  will  assist  in  the  presentation  of  the  subject  and  have  drawn 
largely  from  the  papers  of  Prof.  Roemer  in  the  "Beitrage  zur  Klinik  der 
Tuberculose." 

One  of  the  most  startling  discoveries  of  recent  years  is  the  proof  that 
tuberculosis,  like  all  other  contagious  diseases,  is  one  of  childhood  and  much 
of  the  exemption  from  its  fatal  consequences  later  in  life  is  due  to  the 
establishment  of  a  more  or  less  complete  immunity  coupled  with  the  pro- 
nounced natural  resisting  and  recuperative  power  that  is  noticeable  in  child- 


F.  LYLE 


hood  and  continues  during  the  period  of  growth.  The  proof  that  tubercu- 
losis is  almost  universally  disseminated  and  that  infection  occurs  early  in 
life  is  shown  by  the  post-mortem  findings  and  tuberculin  tests  made  in  many 
lands.  As  autopsy  findings  coupled  with  cultural  investigations  furnish  in- 
controvertable  proofs,  it  will  be  well  to  consider  them  first  and  also  take 
their  results  as  a  basis  to  estimate  the  value  of  the  less  positive  tuberculin 
tests.  The  most  recent  and  authoritative  are  those  made  by  Rothe,  under 
the  auspices  of  the  Robert  Koch  Fund  for  the  Conquest  of  Tuberculosis 
at  the  Institute  for  Infectious  Diseases  in  Berlin. 

Out  of  one  hundred  non-selected  cases  dying  consecutively  of  various 
acute  contagious  diseases,  the  majority  of  the  children  being  under  two 
years  of  age  and  none  over  five,  it  was  found  that  21  per  cent,  were  tuber- 
culous; the  findings  were  confirmed  by  the  inoculation  of  guinea  pigs. 
Gafifky,  in  a  previous  investigation  in  which  three  hundred  children  were 
examined,  found  tuberculosis  present  in  fifty-seven.  The  work  of  these  in- 
vestigators shows  that  about  20  per  cent,  of  the  children  under  five  years 
of  age,  dying  from  various  acute  diseases  in  P.erlin,  had  tuberculosis  of 
the  bronchial  or  mesenteric  glands. 

As  the  death  rate  from  tuberculosis  in  Berlin  is  less  than  that  of  Cincin- 
nati (Berlin,  20.4  per  10,000;  Cincinnati,  23.3),  we  are  justified  in  conclud- 
ing that  our  children  are  infected  to  an  ecjual  degree. 

Hutinel,  in  1895-6,  in  220  autopsies  of  children  between  one  and  two 
years  of  age,  found  tuberculosis  present  in  ii  per  cent. 

Kuss,  in  1895-6,  obtained  the  following  results :  Nothing  to  three  months 
of  age,  1.16  per  cent,  tuberculous;  three  to  twelve  months  of  age,  13  per 
cent,  tuberculous ;  two  to  four  years  of  age,  50  per  cent,  tuberculous. 

Landouzy  has  found  that  among  children  dying  before  the  second  year : 
One  in  seven  and  one-half  die  of  tuberculosis;  one  in  si.x  die  of  tuberculosis 
between  birth  and  one  year ;  one  in  four  die  of  tuberculosis  between  one  and 
two  years  of  age;  one  in  three  die  of  tuberculosis  between  two  and  five  years 
of  age. 

While  these  figures  are  obtained  from  hospital  material  in  which  tuber- 
culosis is  very  prevalent,  they  are  significant  and  show  that  the  fatality  from 
the  disease  increases  until  the  third  year. 

Bollinger  and  Mueller,  in  500  autopsies  made  in  the  years  1881-8,  ob- 
tained the  following  results :  Nothing  to  one  year,  12.25  per  cent,  tuber- 
culous ;  one  to  two  years,  28.5  per  cent,  tuberculous ;  two  to  three  years,  36.9 
per  cent,  tuberculous;  four  to  five  years,  61.9  per  cent,  tuberculous;  six  to 
ten  years,  40  to  50  per  cent,  tuberculous ;  ten  to  eleven  years,  85  per  cent, 
tuberculous. 

Recently  Benjamin  and  Sluka  have  reported  the  following:  Nothing  to 
three  months,  6  per  cent,  tuberculous ;  three  to  six  months,  17  per  cent,  tuber- 
culous; six  to  twelve  months,  22  per  cent,  tuberculous;  one  to  two  years, 
42  per  cent,  tuberculous. 

Comby,  at  the  Congress  in  Washington,  reported  1,447  autopsies,  in  536 

Page  S23 


RAXSOHOFF  MEMO  RIAL  VOLUME 


of  which  tuberculosis  was  found.  His  figures  are  as  follows :  Four  tuber- 
culous in  316  autopsies  of  children  nothing  to  two  months  of  age,  2  per  cent. ; 
39  tuberculous  in  217  autopsies  of  children  three  to  six  months  of  age,  18 
per  cent.;  69  tuberculous  in  254  autopsies  of  children  six  to  twelve  months 
of  age.  27  per  cent.;  141  tuberculous  in  327  autopsies  of  children  one  to 
two  years  of  age,  43  per  cent. 

Hamberger  obtained  9  per  cent,  of  positive  results  in  children  under  two 
years  of  age :  Ranza  found  14  per  cent.,  and  Paisseau  and  Tixier,  in  the 
Paris  clinic,  obtained  the  following:  From  birth  to  three  months.  164  cases. 
12  positive.  7.7  per  cent.;  three  months  to  two  years,  666  cases,  141  positive. 
21  per  cent. 

The  latter  have  found  that  the  results  of  the  test  in  very  young  childrea 
are  not  reliable.  They  obtained  six  positive  reactions  from  ten  tuberculous 
children  under  three  months  of  age.  They  find  the  results  of  their  test  cor- 
respond closely  to  the  post-mortem  findings  of  Kuss. 

Cohn"  has  shown  the  reaction  to  be  much  more  frequent  in  children 
living  in  a  tuberculous  environment.  By  means  of  the  Pirquet  test  in  273 
children  of  tuberculous  parents  he  obtained  the  following:  Two  to  three 
years  old.  66  per  cent,  of  positive  reactions;  four  to  five  years  old,  66  per 
cent,  of  positive  reactions ;  six  to  seven  years  old,  77.5  per  cent,  of  positive 
reactions ;  eight  to  nine  years  old,  77  per  cent,  of  positive  reactions ;  ten  to 
eleven  years  old,  80.5  per  cent,  of  positive  reactions;  twelve  to  thirteen  years 
old,  89.9  per  cent,  of  positive  reactions;  fourteen  years  old.  100  ]ier  cent,  of 
positive  reactions. 

Pollok  found  97.6  per  cent,  of  the  children  in  a  tuberculous  environment 
reacted,  and  even  96  per  cent,  of  those  two  years  of  age  were  positive.  These 
results  strengthen  the  views  of  many  authors  that  the  opportunities  for 
tuberculosis  infection  are  as  prevalent  in  the  homes  of  the  rich  as  in  the 
rooms  of  the  poor ;  when  the  babies  live  in  proximity  to  a  phthisical  mother, 
a  father  with  chronic  bronchitis,  or  a  grandparent  with  emphysematous 
asthma,  the  conditions  resemble  those  employed  for  the  experimental  inocu- 
lation of  tuberculosis. 

Calmette  has  found  that  the  infants  thus  exposed  to  repeated  and  severe 
infections  give  the  following  percentage  of  reactions:  9  per  cent,  between 
birth  and  the  first  year;  22  per  cent,  between  one  and  two  years;  53  per 
cent,  between  two  and  five  years ;  81  per  cent,  between  five  and  fifteen  years ; 
87  per  cent,  after  the  fifteenth  year. 

In  Kasanlik.  during  the  past  five  years,  ninety-seven  males  have  died 
of  tuberculosis;  of  these,  25.7  per  cent,  were  under  fifteen  years  of  age  and 
74.3  per  cent,  over ;  of  the  latter,  22.2  per  cent,  were  married ;  62  per  cent. 
of  these  had  children,  and  their  influence  upon  them  may  be  given  as  fol- 
lows: 9.9  per  cent,  died  before  the  end  of  the  first  year;  19.9  per  cent,  died 
between  the  first  and  second  years;  30.7  per  cent,  died  between  the  second 
and  third  years;  39.6  per  cent,  were  living  after  the  third  year. 

Pat/c  32', 


B.  F.  LYLE 

Children  of  tuberculous  mothers :  Of  the  married  women,  33.2  per  cent, 
had  been  pregnant.  The  children  can  be  classified  as  follows:  16.2  per  cent, 
died  between  birth  and  the  first  year;  32.4  per  cent,  died  between  the  first 
and  second  year;  16.2  |3er  cent,  died  between  the  second  and  third  year;  34.8 
per  cent,  lived  after  the  third  year. 

When  the  father  and  mother  were  tuberculous,  30  per  cent,  of  the  chil- 
dren died  of  various  diseases,  mostly  pneumonia;  60  per  cent,  died  of  tuber- 
culosis between  birth  and  the  third  year;  10  per  cent,  lived  after  the  third 
year. 

Siiiiiiiiary. — \\  hen  the  father  is  tuberculous,  39.6  per  cent,  live  after  the 
tliird  year ;  when  the  mother  is  tuberculous,  34.8  per  cent,  live  after  the  third 
year;  when  both  are  tuberculosis,  10  per  cent,  live  after  the  third  year. 

These  figures  are  sufficient  to  show  the  prevalence  of  tuberculosis  early 
in  life  and  the  reliabilitv  of  the  tuberculin  tests. 


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jtained  by  Calmette  in  Lille  by  the  tuberculin  test.     (Beitrage 
Klinik  der  Tubcrkulose. ) 


We  are  now  ready  to  estimate  the  dissemination  of  tuberculosis  in 
civilized  countries. 

Herford,  from  investigations  made  in  the  public  schools  of  Altoona,  Pa., 
has  shown  by  the  tuberculin  test  a  minimum  of  55  per  cent,  and  a  maximum 
of  78  per  cent,  of  positive  reactions.  The  children  were  not  from  the 
poorer  classes,  but  from  families  in  moderate  circumstances.  The  higher 
figures  were  naturally  obtained  in  those  children  who  were  in  contact  with 
tuberculous  relatives.  He  arrives  at  the  conclusion  that  the  majority  of 
children  are  infected  before  they  enter  school ;  2,598  children  were  tested 
with  20  per  cent,  tuberculin. 

In  Bucharest,  Nicolaesco  and  Nestor  tested  2,000  children  by  the  con- 
junctival method;  between  65  and  66  per  cent,  were  positive. 

Page  32S 


RANSOHOFF  MEMORIAL  VOLUME 


Calmette  got  like  results  from  the  Pirquet  test  in  Lille  in  children  of  the 
working  classes.  They  show  from  birth  to  one  year,  8  per  cent,  positive ;  one 
to  two  years,  28  per  cent. ;  two  to  five  years,  65  per  cent. ;  after  the  sixth 
year,  92  per  cent. 

These  figures,  from  Altoona,  Bucharest  and  Lille,  are  like  those  obtained 
from  Vienna,  Prague,  Danzig,  Paris,  Dusseldorf ,  Berlin  and  Muenchen,  and 
indicate  liow  universal  is  the  saturation  of  children  with  tuberculosis  in 
cities. 

Scheltenia  found  a  somewhat  lower  proportion  in  the  tuberculin  tests 
of  520  children  in  the  Groninger  policlinic.  He  thinks  this  is  due  to  the 
better  character  of  the  dwellings. 

In  this  work  there  has  been  a  noticeable  void  because  of  a  lack  of  investi- 
gations made  in  the  country.  Formerly  we  had  only  the  careful  investi- 
gations  of   Hillenberg,   who.   apparently,   did   not   adopt   the   best   method. 


z 

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T.ABLE  II. — Results  obtained  by  Scheltema  from  the  tuberculin  test  in  Groningen. 
(Beitrage  Klinik  der  Tuberculosa.) 


Jakop  recently  attempted  to  determine  the  extent  of  tuberculosis  in  the 
country  surrounding  Hanover.  He  gave  the  Pirquet  test  to  2,744  children ; 
L927  were  between  six  and  fourteen  years  of  age  and  817  between  six 
months  and  six  years.  The  responses  from  those  attending  school  was  45.9 
per  cent.  In  the  first  year  of  school  it  was  35.6  per  cent.;  in  the  last,  64.1- 
per  cent.  Jakop  gives  no  rea.son  for  inferring  that  the  infection  occurred 
in  school  and  has  concluded  it  was  contracted  at  home  before  attendance  at 
school.  These  figures  also  prove  that  tuberculosis  is  but  little  less  prevalent 
among  the  country  folk  than  among  the  children  in  large  cities. 

The  observations  of  Jakop  are  conspicuous  in  showing  that  when  tuber- 
culosis was  present  in  a  house  the  children  nearly  always  reacted;  again, 


B.  F.  LYLE 

there  were  children  who  reacted  for  whom  he  could  find  no  source  of  infec- 
tion. In  cottages  where  there  had  been  no  one  sick  with  tuberculosis  for 
years  30  to  40  per  cent,  of  the  children  recated.  This  is  a  proof  of  the  re- 
markable diffusion  of  the  yet  unrecognized  occasion  for  infection.  Hillen- 
berg,  in  more  recent  investigations,  obtained  like  results.  He  worked  in  a 
region  where  tuberculosis  was  not  very  prevalent ;  the  mortality  from  tuber- 
culosis being  but  9  per  10,000.  According  to  the  statement  of  Koch  this  is 
the  lowest  in  Germany.  Hillenberg,  in  six  country  areas  with  an  almost 
exclusive  farming  population  and  satisfactory  dwellings,  prosperous  inmates 
and  good  sanitary  arrangements;  for  cleanliness  being  also  fairly  good;  a 
region  where  for  ten  years  there  had  not  been  a  death  from  tuberculosis 
discovered ;  yet  found  25  per  cent,  of  the  school  children  reacted  to  tuber- 
culin. A  source  of  infection  from  coughing  consumptives  was  excluded  and 
likewise  infection  from  cattle.     As  a  result  Hillenberg  came  to  the  conclu- 


% 

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Table  III.— Results  obtained  by  Hilk-nl 
KliniU  de 


rg  in  rural  districts  in  Germany. 
Tuherkulose.) 


(Beitragt 


sion  that  here,  as  in  similar  instances,  the  tubercle  bacilli  in  nature  must 
have  a  wider  scope  than  is  usually  recognized. 

"From  a  practical  epidemiological  standpoint  one  can  hardly  speak  of 
anything  more  than  an  ubiquitous  extension." 

Roemer  believes  it  possible  that  those  infected  with  latent  tuberculosis 
may  be  able  to  spread  the  disease  in  a  manner  that  is  incomprehensible  to  us 
at  the  present  time.  This,  of  course,  is  a  pure  hypothesis  based  upon  the 
results  of  veterinary  practice  and  his  own  observations.  It  can  at  times  be 
shown  that  the  introduction  of  a  tuberculous  cow  into  a  previously  tubercu- 
losis-free stable  leads  to  a  gradual  involvement  of  the  entire  herd  to  the 
extent  that  suddenly  nearly  all  react;  although  this  need  not  indicate  that 

Page   HI 


RANSOM  OFF  MEMORIAL  VOLUME 


the  imported  beast  is  tuberculous  in  a  clinical  sense  if  the  employment  of 
other  means  of  proving  the  presence  of  tubercle  bacilli  are  negative. 

Hillenberg  further  investigated  by  examining  the  remainder  of  the  people 
in  these  communities  and  occasionally,  though  rarely,  found  a  case  of  tuber- 
culosis by  means  of  the  pirquet  test.  He  found  conditions  to  be  as  seen  in 
the  following  diagram.  At  the  conclusion  of  childhood  he  shows  that  36.4 
per  cent,  of  the  children  were  infected.  The  results  in  the  several  regions 
varied  from  10  to  61.7  per  cent.  These  figures  are  lower  than  those  ob- 
tained in  the  large  cities.  It  may  be  observed  that  Hillenberg  carried 
on  his  investigations  by  the  cutaneous  method.  Roemer  believes  that  a  more 
sensitive  method  would  have  shown  a  larger  number  of  positive  findings. 
Hamberger  and  Monti,  when  examining  children  between  the  ages  of  eleven 
to  fourteen,  with  the  cutaneous  method,  got  52  per  cent,  of  positive  reactions, 
but  by  the  united  cutaneous  and  puncture  method  95  per  cent. 


■  X  rMtioi  mot  tn.  uw-ms  -ah  : 
un  T>3  luTio  or  tkk  LAinK.-  lo 


.K  I\'. — Showing  comparati 


mortality  from  tuberculosis  in  Li 
periods. 


at  various 


In  Nothmann's  investigations  positive  results  were  increased  in  263  cases 
from  47.1  per  cent,  by,  the  cutaneous  method  to  77  per  cent,  by  the  stick- 
method.  Even  if  the  experiments  of  Hillenberg  in  the  sparsely  tuberculous 
areas  indicate  that  the  degree  of  involvement  is  not  so  great  as  in  the  large 
cities,  we  learn,  on  the  other  hand,  the  surprising  fact  that  even  in  those 
places  where  tuberculosis  is  so  rare  opportunities  for  infection  must  be  at 
the  same  time  considerable. 

The  enormous  percentage  of  reactions  that  may  be  obtained  in  the  chil- 
dren in  a  tuberculous  environment  is  shown  by  the  comparative  tables  ot 
Cohn. 

All  these  results  strengthen  the  view  that  the  opportunities  for  infection 
are  so  widespread  that,  at  least  in  neighborhoods  with  a  high  morbidity  from 

Page  328 


B.  F.  LYLE 


tuberculosis,  all  children  at  the  termination  of  childhood  will  be  infected 
with  tuberculosis. 

If  it  is  a  fact  that  this  tuberculosis  saturation  is  almost  universal  so  early 
in  life,  it  will  be  interesting  to  know  why  the  period  of  greatest  mortality 
is  so  far  removed ;  at  least  a  score  of  years. 

That  this  is  true  is  seen  by  our  own  records  and  those  of  other  countries. 
Infection  that  is  severe  enough  to  be  manifest  almost  invariably  leads  to  n 
fatal  ending  if  it  occurs  before  the  first  year ;  after  this  there  is  a  period  of 
fifteen  years  when  the  mortality  from  the  disease  is  comparatively  slight, 
although  tuberculin  tests  prove  the  presence  of  tuberculosis  in  a  latent  state. 

This  condition  is  not  without  advantage  to  the  individuals  infected,  for 
we  learn  from  animal  experimentation,  clinical,  epidemiological  and  statis- 
tical findings  that  protection  is  thus  aiTorded  against  a  further  tuberculous 
infection  and  an  immunity  is  established  of  a  greater  or  less  degree,  which, 
in  the  majority  of  cases,  confers  e.xemption  for  life  from  the  serious  conse- 
quences of  the  disease;  and,  in  the  majority  of  the  others,  the  clinical  course 
and  pathologic  lesions  are  so  changed  that  we  find  the  duration  of  the  disease 
much  longer  and  the  anatomical  appearances  entirely  different  from  those 
characteristic  of  acute  tuberculosis. 

It  may  be  of  value  for  us  to  here  consider  more  fully  the  advantages  we 
thus  enjoy  from  a  danger  from  reinfection  and  the  effects  of  more  acute 
and  fatal  forms  of  the  disease. 

A  number  of  experiments  have  been  made  on  animals,  ranging  from 
guinea  pigs  to  monkeys,  to  learn  the  degree  of  resistance  of  the  tuberculous 
to  a  further  implantation  of  germs. 

The  experiments  made  upon  cattle  some  time  ago  by  Marburger  prove  that 
an  artificial  infection  with  virulent  tubercle  bacilli  confers  immunity  against  a 
new  infection.  These  facts  have  been  recently  confirmed  and  strengthened 
by  Finzi  in  experiments  upon  eight  calves  suffering  from  spontaneous  tuber- 
culosis. These  experiments  are  important  as  they  confirm  the  findings  made 
upon  artificially  infected  animals. 

The  same  results  were  obtained  previously  by  Vallee  and  Calmette  ana 
finally  Roemer  has  shown  there  can  be  no  doubt  as  far  as  animal  experi- 
mentation can  show  that  an  existing  infection,  either  natural  or  artificial,  is 
a  protection  against  further  infection.  He  first  inoculated  guinea  pigs,  but, 
because  of  their  great  susceptibility,  concluded  his  experiments  with  sheep. 
He  finds,  however,  the  immunity  is  only  relative  and  a  very  heavy  assault 
can  cause  the  immune  body  to  succumb,  even  if  at  a  much  slower  rate  than 
occurs  in  the  non-immune  animal. 

It  is  now  proven  by  animal  experimentation,  and  confirmed  by  a  large 
series  of  statistics,  that  a  strong  infection  in  a  partially  immune  organism 
leads  to  forms  of  tuberculosis  that  are  entirely  different  from  the  results  of 
a  primary  infection,  and  it  is  because  of  this  that  human  tuberculosis  can 
clinically  and  anatomically  exhibit  very  dissimilar  disease  aspects ;  the  view 
is  also  permissible  that  through  this  strong  immunity  the  organism  can  over- 

Page  S.iO 


RANSOHOFF  MEMORIAL  VOLUME 


come  a  severe  infection.  Roenier  believes  it  must  be  accepted  that  the 
effectual  reinfection  leading  to  phthisis  does  not  originate  outside,  but  must 
be  already  present  in  tuberulous  foci ;  in  other  words,  it  is  a  metastatic  auto- 
inoculation.     There  are  difficulties  in  explaining  these  conditions. 

A  reinfection  that  may  be  interrupted  in  adults  results  in  a  child  in  a 
marked  degree  of  involvement.  Roemer,  in  co-operation  with  Joseph,  has 
established  that  the  immunity  of  tuberculous  individuals  against  a  new  in- 
fection in  many  cases  does  not  depend  upon  a  destruction  of  the  newly  intro- 
duced bacilli;  at  least,  in  animals  proven  to  be  immune  by  reinfection,  living 
bacilli  could  be  shown  at  the  place  of  inoculation.  Again,  the  serum  of 
highly  immunized  sheep  was  not  able  to  destroy  the  tubercle  bacilli  in  a 
single  instance  under  favorable  conditions. 

Roemer  believes  the  immunity  to  be  a  labile  one  and  resembles  the  form 
of  immunity  we  see,  for  example,  in  the  perophasmodium  of  cattle  (Texas 
fever).  Animals  that  have  overcome  the  acute  infection  remain  infected 
with  the  living  virus  but  are  immune  to  a  new  infection  and  can  remain  with- 
out danger  in  infected  meadows. 

We  must  presume  that  tuberculosis  immunity  is  specific  in  nature, 
although  not  marked  as  in  the  cases  of  more  acute  diseases:  the  intensity 
of  immunity  usually  being  in  proportion  to  the  sensibility  of  the  individual 
to  the  contagion. 

The  fact  that  tuberculosis  is  a  disease  usually  contracted  early  in  life 
makes  the  environment  the  chief  predisposing  factor.  Investigations  have 
shown  that  in  50  per  cent,  of  the  active  cases  of  tuberculosis  in  children  a 
parent  had  open  tuberculosis. 

What  had  been  regarded  as  predisposing  factors  in  the  causation  of  the 
disease  we  may  now  consider  agencies,  which,  by  reducing  the  inherent  or 
acquired  immunity,  permit  what  would  be  a  latent  process  to  become  active. 
If  we  were  to  attempt  to  individualize  these  pernicious  agencies,  although 
they  are  characterized  by  team  work,  half  a  dozen  or  more  could  be  selected, 
any  one  of  which  is  sufficiently  important  to  be  considered  the  principal  and 
all  must  receive  practical  attention  before  the  dawn  of  the  non-tuberculosis 
era.  Without  attempting  to  cover  the  field  we  may  mention  poverty,  alco- 
holism, the  location  and  character  of  dwellings  and  shops,  unsanitary  occu- 
pations, particularly  those  of  the  "blind-alley"  kind;  child  labor  and  long 
hours  of  labor. 

These  are  factors  because  of  the  chronic  nature  of  tuberculosis.  They 
are  not  predisposing  causes,  except  in  so  far  as  they  may  be  instrumental  in 
increasing  the  sources  of  contagion.  Ignorance  and  overcrowding  are  im- 
portant but  not  essential  factors  in  all  contagious  diseases.  It  is  interesting 
to  notice  the  influences  attributed  to  heredity  at  different  times.  At  first  it 
was  regarded  as  the  most  important  element  in  the  origin  of  the  disease; 
then  it  was  maintained  that  a  peculiar  vulnerability  of  a  specific  character 
was  transmitted  from  parent  to  child ;  today  it  is  regarded  of  importance 
because  of  the  immunizing  capabilites  that  are  transmitted.    The  individual 

Page  330 


B.  F.  LYLE 

is  not  supposed  to  be  protected  from  the  infection,  but  is  shielded  by  a  partial 
immunity  manifested  by  a  difference  in  the  nature  of  the  lesions  induced; 
they  being  of  a  much  more  chronic  type ;  the  life  of  the  victim  is  thus  fre- 
quently spared  at  a  cost  of  physical  vigor  and  frequently  he  is  held  as  a 
hostage  for  the  dissemination  of  the  germs.  That  the  influence  of  heredity 
is  potent  is  attested  by  many  recent  investigations.' - 

We  are  therefore  forced  to  the  conclusion  from  a  study  of  the  relative 
mortality  from  the  disease  and  the  variety  of  its  manifestations  in  various 
peoples  and  races  that  heredity  must  play  an  important  part  in  determining 
the  character  of  the  lesions  and  the  percentage  of  mortality.  We  find  this 
is  also  true  of  the  contagious  exanthemata;  the  Chinese  and  Japanese  being 
exempt  from  scarlet  fever,  while  the  natives  of  newly  discovered  islands  die 
in  great  numbers  when  they  are  first  infected  with  hitherto  unknown  con- 
tagious diseases.  The  Jewish  people  from  a  long  familiarity  with  tuber- 
culosis enjoy  a  comparative  immunity  from  its  fatal  consequences,  although 
they  evidently  possess  no  exemption  from  manifest  infection. 


jHr — r 

/lii— X-:! 


Table  V. — Showing  the  relative  proportion  of  the  acute  and  chronic  forms  of  tubercu- 
losis at  various  ages  in  civilized  countries.     (Eeitrage  Khnik  der  Tuberkulose.) 


Rothe  is  of  the  opinion  that  the  early  infection  results  in  the  establish- 
ment of  an  immunity  that  protects  the  majority  of  persons  from  any  further 
manifestations  of  the  disease  and  in  others  leads  to  a  marked  prolongation 
of  the  evolution  of  the  pathologic  process.  He  believes  that  as  in  syphilis 
we  find  various  phenomena  making  their  appearance  in  a  fairly  orderly  suc- 
cession, due  to  the  gradual  involvement  of  tissues  that  at  first  were  invulner- 
able, so  in  tuljerculosis  do  we  find  a  like  condition. 

Thus,  we  can  dififerentiate :  First,  a  stage  of  generalization  (glandular 
tuberculosis)  having  an  origin  directly  from  the  infection;  second,  a  stage 
of  hematogenous  dissemination,  characterized  by  scrofula  and  bone  and  joint 
involvement;  later,  we  have  phthisis  with  its  sequelae,  involvement  of  the 
larynx  and  intestines  and  other  organs. 


RANSOHOFF  MEMORIAL  VOLUME 


That  exeiiiinioii  from  the  more  acute  extensive  tuberculous  processes 
characteristic  of  the  disease  in  the  non-immune  individual  is  due  to  the  pro- 
tection secured  early  in  life  is  shown  by  the  clinical  aspects  of  the  disease 
in  sparsely  settled  countries  and  among  those  races  which  have  but  recently 
been  brought  in  contact  with  the  disease. 

If  the  tuberculosis  does  not  cause  a  rapid  death  it  leads  to  increased  re- 
sistance against  tuberculous  infection,  thus  preventing  contagion  from  the 
outside  later  in  life.  The  degree  of  immunity  is  not  sufficient  to  destroy  the 
bacilli  present  and  the  involvement  of  organs  later  must  be  the  result  of 
auto-infection.     We  have  an  analogy  of  this  in  malaria. 

Roemer  ap|)roves  of  the  conclusions  of  Hamberger,  whose  observations 
showed  that  after  a  reinfection  of  guinea  pigs  the  place  of  inoculation  re- 
mains for  a  long  period  reactionless ;  but,  however,  when  for  any  reason 
the  immunity  is  lost,  even  after  a  series  of  months,  the  hitherto  weakened 
tubercle  bacilli  gain  the  upper  hand  and  cause  an  exacerbation  of  the  tuber- 
culous processes. 

Numerous  individuals,  in  spite  of  such  reinfection,  do  not  become  phthisi- 
cal. There  is  also  reason  for  maintaining  that  certain  groups  of  individuals 
are  also  immune  to  tuberculosis.  It  is  no  doubt  true  that  children  who  suf- 
fered from  a  relatively  severe  infection  in  childhood  are  more  prone  to  posi- 
tive results  later  in  life,  due  to  metastatic  auto-inoculation. 

In  1908-10.  Freymuth  examined  the  histories  of  1,400  adults  and  328 
children ;  as  a  result,  he  came  to  the  important  practical  conclusion  that  it 
can  not  be  acknowledged  that  there  is  any  necessity  for  the  separation  of 
open  and  closed  cases  in  a  sanatorium. 

The  most  startling  investigation  in  this  line  is  the  work  of  the  Japanese, 
Kurashige,  who.  by  means  of  a  modified  anti-formin  process,  found  bacilli 
in  the  blood  of  155  tuberculous  patients  in  various  stages;  not  only  this,  but 
in  twenty  of  thirty-four  investigations  of  clinically  healthy  adults  (59  per 
cent.)  he  found  tubercle  bacilli  in  the  blood.  In  four  the  findings  were  con- 
firmed by  inoculations  in  guinea  pigs.  These  results  were  confirmed  by 
Luzuki  and  Takaki,  who  found  tubercle  bacilli  in  the  blood  of  509  out  of  517 
tuberculous  patients  and  in  twenty-eight  out  of  fifty-four  clinically  healthy 
men.  These  twenty-eight  gave  a  positive  Pirquet  and  in  none  of  those  who 
did  not  react  were  the  bacilli  found  in  the  blood. 

This  shows  the  fallacy  of  the  old  belief  that  bacilli  in  the  blood  leads  to 
miliary  tuberculosis.  It  shows  there  is  no  correspondence  in  the  results  of 
the  inoculation  of  normal  animals  and  those  who  are  already  infected.  Acs- 
Nagy,  months  before  the  demise  of  patients,  found  tubercle  bacilli  in  the 
blood  without  miliary  tuberculosis  resulting.  It  has  been  maintained  that 
the  ])rogression  of  the  bacilli  in  the  various  organs  varies  greatly,  according 
as  the  implantation  is  introduced  into  a  normal  individual  or  into  one  with 
tuberculosis.     This  is  shown  by  epidemiologic  examinations. 

Page  SiZ 


B.  F.  LYLE 


PART  TI. 
In  countries  in  which  there  is  a  comparatively  shght  amount  of  tubercu- 
losis in  adults  we  more  frequently  see  the  more  acute  forms  of  tuberculosis 
characteristic  of  childhood. ■  In  this  connection  the  observations  of  Deyckes 
in  Turkey,  of  Romer  and  Nine  in  Argentina,  and  of  Westenhoefifer  in  Chili, 
are  confirmatory.  In  autopsies  made  by  the  latter,  in  Santiago  in  1908-9, 
he  found  the  dissemination  of  tuberculosis  to  be  much  less  than  is  seen 
in  the  post-mortems  of  European  pathological  institutions.  Not  more  than 
half  the  amount  was  found  and  there  was  a  remarkable  difference  seen  in 
the  forms  of  the  disease.  In  forty-five  who  had  died  of  pulmonary  tuber- 
culosis only  twenty-eight  had  the  chronic  form  and  even  in  these  there  was 
a  failure  of  connective  tissue  formation  and  large  cavities.  The  majority 
of  the  cases  were  of  confluent  caseous  pneumonia,  a  form  of  tuberculosis 
we  are  accustomed  to  see  in  the  children  of  Europe.  Westerhoefifer  says 
that  at  least  one-third  of  the  cases  are  of  very  acute  forms.  He  ascribes  this 
difference  to  the  fact  they  have  not  had  the  early  protection  of  a  latent  form 
acquired  in  childhood. 


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Tahi.E  VI. — .After  Escherich.     Showing  the  relative  mortality  and  morbidity  in  children 
in  Vienna  in  1909.     ( Wien.  med.  Woch.) 


In  support  of  this  the  observations  of  Metschnikofif,  Burnet  and  Tarasse- 
vitch,  made  in  Russia,  are  important.  They  found  that  the  sons  of  Calmuck 
families,  when  sent  to  the  more  advanced  schools  of  Astrakan,  died  at  an 
astonishing  rate  from  acute  tuberculosis.  Phthisis  was  relatively  rare.  Like 
observations  were  made  by  Metschnikofif  and  others  in  Austria  which  show 
that  in  the  regiments  sent  from  Bosnia  and  Herzegovina  the  soldiers  died 
with  greater  relative  frequency  from  tuberculosis,  notwithstanding  the  fact 
that  the  disease  is  not  very  prevalent  in  their  own  provinces. 

These  observations  help  us  to  solve  a  problem  with  which  Koch  was  busy 
in  his  last  years.  It  is  known  that  in  Germany  and  in  other  civilized  coun- 
tries the  death  rate  from  tuberculosis  has  decreased  since  1880,  while  in 
Norway,  Ireland  and  Japan   it  has  increased.     The  above  epidemiological 


RAXSOHOFF  MEMORIAL  VOLUME 


experiments,  taken  with  the  tuberculosis  immunity  observations,  offer  the 
key  to  the  still  unsolved  problem. 

"The  less  prevalent  tuberculosis  is  among  a  people  the  greater  is  the 
toxicity  of  the  disease."  That  is,  increased  mortality  to  morbidity.  This 
indicates  the  presence  of  the  more  severe  acute  forms  of  the  disease  in  a 
slightly  contaminated  population,  either  from  rarity  or  failure  of  the  milder 
chronic  phthisi. 

As  a  result  we  may  express  the  formula,  "The  more  widely  spread  the 
tuberculous  infection  the  less  the  relative  mortality."  The  meaning  of  these 
two  precepts  is  appreciable  when  we  remember  the  facts  tuberculosis  im- 
munity represent ;  that  is,  keep  in  mind  that  the  tuberculous  individual  is  ap- 
parently protected  from  outside  new  infections.  The  auto-infection  from 
within,  even  if  severe,  shows  there  is  a  relative  immunity  in  that  not  a  gallop- 
ing consumption  but  a  chronic  phthisis  ensues. 

By  means  of  this  resistance  in  those  countries  in  which  tuberculosis  is 
the  most  extensive;  in  which  tuberculous  saturation  has  reached  its  highest 
tide,  the  mortality  rate  from  tuberculosis  had  materially  declined. 

The  accompanying  charts,  showing  the  tuberculosis  record  of  Hamburg 
for  the  last  ninety  years,  proves  this  conclusively. 

Of  course,  we  are  apt  to  consider  that  the  significant  and  remarkable 
changes  in  the  mortality  rates  of  an  epidemic  scourge  depend  upon  artificial 
influences  and  it  is  humanly  comprehensible  that  even  medicine  is  willing  to 
claim  that  the  credit  for  these  improvements  is  due  to  her  own  scientific 
acquisitions. 

No  doubt,  however,  were  the  history  of  plagues  better  known  and  the 
variations  in  the  intensity  of  infectious  diseases  better  comprehended  we 
would  not  agree  too  lightly  to  such  claims. 

We  are  reminded  here  of  the  disappearance  of  the  plague  from  Europe 
at  the  beginning  of  the  eighteenth  century,  the  reason  for  which  is  not  clearly 
understood,  and  remember  how  often,  still  earlier,  when  the  epidemic  was 
absent  for  one  to  ten  years,  in  every  instance  the  methods  employed  were 
promptly  credited  as  the  cause.  We  are  cognizant  of  the  remarkable  changes 
in  the  mortality  rate  of  smallpox  in  very  recent  years.  Finally,  we  may 
refer  to  the  experiences  of  life  insurance  companies  obtained  in  an  experi- 
mental way.  They  do  not  reject  individuals  who  are  free  from  a  history  of 
hereditary  tuberculosis  and  whose  personal  record  is  clear  when  they  are 
living  or  have  lived  with  a  tuberculous  partner.  Little  regard  is  paid,  at 
least  in  Germany,  to  the  danger  of  an  adult  living  with  a  tuberculous  mate, 
and  one  can  not  accuse  the  insurance  coinpanies  of  being  careless. 

In  conformity  with  this  is  the  record  of  so  experienced  a  physician  in 
tuberculosis  as  Petruschky.  When  mentioning  the  dangers  that  marriage 
brings  to  the  tuberculous  he  touches  upon  the  danger  of  infection  through 
the  tuberculous  partner  and  states  as  laconically  as  impressively :  "From  re- 
ports not  yet  observed."  In  this  connection  we  can  state  that  before  the  dis- 
covery of  the  tuberculous  germ  many  physicians  did  not  believe  in  the  con- 

Page  Ui 


B.  F.  LVLE 


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-  =  =  -Tit=E-rEEE|:  =  ^i-5 

-=  =  --— -^ :;;; 

,906 

Table  VII  —Showing  progressive  decrease  in  mortality  from   tuberculosis  in  Hamburg  during 
the  past  ninety  years.  (Beitragc  Klinik  der  Tuberkulose.) 


RAXSOHOFF  MEMORIAL  VOLUME 


tagioiisness  of  tuberculosis  because  they  saw  many  persons  remain  in  close 
contact  with  consumptives  without  apparent  injury. 

In  striking  contrast  to  this  are  the  recently  reported  investigations  of 
Jakob,  made  in  a  badly  infected  region  in  the  neighborhood  of  Osnabruck. 
He  mentions  the  danger  that  might  arise  through  dwellings  and  makes  the 
following  observations:  The  wife  of  a  healthy  man  died  of  consumption. 
Some  time  after  he  married  again  and  this  wife  died  from  the  same  disease. 
The  same  occurred  with  the  third  and  fourth  wives.  Jakob  thinks  this  re- 
sulted from  a  house  infected  with  tuberculosis.  It  is  remarkable  that  the 
husband  remained  well  in  the  house  and  Jakob  states  he  has  never  seen  the 
second  husband  of  a  healthy  wife  die  of  consumption  whose  first  husband 
had  died  from  the  disease. 

Metschnikoff,  Burnet  and  Tarassevitch,  in  the  report  of  their  work,  men- 
tion a  similar  observation. 

One  of  the  authors  of  the  book  lived  for  a  year  with  his  wife,  who  had 
a  fatal  form  of  consumption,  without  contracting  the  disease. 

Why  is  it  that  a  house  that  is  infected  sufficiently  to  be  fatal  to  the  in- 
coming wives  was  not  fatal  to  the  husband? 

It  may  be  remarked  that  Jakob  indicates  the  marked  prevalence  of  tuber- 
culosis in  the  people  of  this  region,  so  that  it  is  plausible  that  the  man  in 
every  instance  had  married  an  infected  woman  in  whom  pregnacy,  child- 
birth and  the  puerperal  state  had  favored  the  progress  of  the  disease.  The 
objection  that  it  was  a  peculiar  coincidence  that  a  man  should  marry  a  tuber- 
culous woman  in  every  instance  appears  out  of  place.  The  consumptive 
\'enus  of  Botticelli  was  regarded  for  years  as  the  ideal  of  a  perfect  female 
form;  therefore,  why  should  there  not  today  be  an  individual  who  ignorantly 
and  fatefully  turns  only  to  a  consumptive  type?  Finally  it  must  be  men- 
tioned that  Jakob,  as  a  result  of  his  careful  research,  is  of  the  opinion  that 
the  infection  during  childhood,  as  a  rule,  potently  influences  the  after-life 
of  some  persons. 

The  fact  thus  proven  by  clinical,  epidemiological  and  statistical  investi- 
gations that  adults  enjoy  an  appreciable  or  even  absolute  protection  against 
a  new  infection  from  without  emphasizes  the  fact  that  when  children  they 
had  a  mild  infection. 

What  shall  we  say  about  the  tuberculosis  situation  in  Cincinnati  ?  What 
are  the  results  of  the  measures  that  have  been  employed?  What  course 
shall  be  pursued  in  the  future  ? 

In  the  decade,  1901  to  1910,  the  death  rate  in  the  United  States  from 
tuberculosis  declined  from  196.9  for  each  100,000  to  160.3,  a  decrease  of 
over  18  per  cent.;  while  the  general  death  rate  from  all  causes  declined  only 
half  as  mucli.  at  the  rate  of  9.7  per  cent.,  or  from  1655.0  to  1495.0  per 
100,000. 

We  are  informed  by  Dr.  Maurice  Fisher  that  in  Germany  within  the  last 
five  years  the  mortality   from  tuberculosis  has  ceased  to  fall. 

Page  3.% 


F.  LYLE 


Prof.  Walter  F.  Wilcox,  of  Cornell,  consulting  statistician  of  New  York 
State,  in  his  reports  for  the  years  1909  and  1910,  states  that  the  campaign 
against  tuberculosis  has  as  yet  made  no  change  in  the  tuberculosis  mortality 
nf  New  York  State. 

A  glance  at  the  death  statistics  of  our  city  shows  that  the  mortality  from 
tuberculosis  bears  a  certain  relation  to  the  general  death  rate.  In  other 
words,  any  measure  or  condition  that  influences  the  death  rate  in  the  city 
has  a  proportionate  effect  upon  that  from  tuberculosis.  The  rate  among 
children  seems  to  be  greatly  reduced.  This  seems  somewhat  remarkable 
when  we  bear  in  mind  the  results  of  the  observatiohs  of  Landouzy  and  other 
Continental  writers,  although  they  correspond  to  the  observations  noted  re- 
cently in  Switzerland. 

It  is  very  difticult  for  us  to  determine  the  mortality  from  tuberculosis 
among  children  previous  to  the  beginning  of  this  century,  owing  to  the  fact 

Tuberkulosesferblichkeil  m  dcr  Sfadt  Hamburg. 
Auf  Je  1000  Lebvnde  derselben  AlUrskiasse 
Slarban  im  AUer  von 
c-i-ij.  -  u-N-M-joJ.  JO  —  »oJ     50—  loj  ub«noJahre    ,,_ 


, 

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S;..-rr^.  1872-1898. 


rrr.  1899 -1910. 


Tabi.k  VIII. — Showing  the  influence  on  adult  mortality  of  tuberculosis  at  various 
periods.     (Beitrage  Klinik  der  Tuberkulose. ) 

that  our  health  office  reports  show  that  about  the  year  1880  hydrocephalus 
prevailed  to  a  great  extent  and  was  classified  as  tuberculosis.  Ten  years  later 
this  uncertain  term  had  given  place  to  marasmus. 

Prof.  P.  G.  Woolley,  who  kindly  glanced  over  the  statistics,  advised  the 
exclusion  from  the  list  of  deaths  from  tuberculosis  those  which  were  at- 
tributed to  these  causes  in  children  under  one  year  of  age. 

In  the  first  period  shown  no  records  can  be  found  of  extra-pulmonary 
forms  of  tuberculosis.  The  same  proportion  as  given  in  the  following  de- 
cade was  used  in  order  to  obtain  an  approximate  estimate  of  the  total  deaths 
from  tuberculosis. 

In  order  to  make  the  estimate  as  reliable  as  possible  the  records  of  the 
census  years  and  the  two  years  preceding  and  following  were  taken  and 


RANSOHOfF  MEMORIAL  VOLUME 


the  average  employed.  The  great  mutations  seen  make  this  necessary  if  we 
aim  to  secure  reliable  data. 

These  statistics  show  that  the  general  death  rate  in  our  city  has  been 
progressively  reduced,  no  doubt  due  largely  to  the  diminution  of  the  mor- 
tality among  children. 

The  present  tuberculosis  death  rate  is  higher  than  that  of  the  previous 

Table  Shozving  Death  Rates  for  Census  Years  and  the  Two   Years  Preceding  and 
Following,  with  Averages. 


. 

of  children 

To 

,a> 

niimbei 

ol 

deaths 

from 

tulierciil 

•s 

- 

g 

^ 

J 

g 

>• 

.- 

i. 

- 

-, 

"■• 

- 

1868 

4424 

443 

1869 

3740 

447 

1870 

3978 

58' 

1871 

5291 

580 

1872 

5116 

616 

Av. 

4510 

*576 

534 

*42 

1878 

4823 

705 

659 

46 

52 

22 

10 

17 

1879 

5290 

740 

698 

42 

55 

22 

9 

5 

1880 

5177 

771 

720 

51 

53 

]/ 

17 

8 

1881 

6110 

997 

9m 

93 

81 

38 

14 

14 

1882 

6873 

846 

783 

63 

59 

26 

17 

17 

Av. 

5653 

812 

753 

59 

60 

25 

13 

12 

1888 

5994 

903 

746 

157 

75 

20 

21 

18 

1889 

5922 

878 

731 

147 

60 

28 

12 

16 

1890 

6441 

913 

7.S6 

157 

58 

97 

15 

19 

1891 

6635 

700 

643 

46 

26 

18 

12 

1892 

6015 

817 

647 

100 

61 

31 

13 

14 

Av. 

6201 

842 

704 

138 

60 

-25 

16 

16 

1898 

5885 

729 

642 

87 

22 

16 

16 

14 

1899 

6000 

804 

692 

112 

39 

21 

7 

14 

1900 

5412 

714 

635 

79 

24 

16 

q 

1901 

6155 

822 

742 

80 

14 

19 

14 

9 

1902 

5744 

736 

647 

89 

22 

14 

3 

11 

Av. 

5839 

761 

672 

89 

24 

17 

10 

11 

1908 

6449 

952 

860 

92 

21 

13 

10 

13 

1909 

.5921 

947 

850 

97 

39 

20 

9 

12 

1910 

6330 

1025 

912 

113 

35 

19 

12 

12 

1911 

6225 

986 

876 

110 

13 

10 

13 

1912 

6453 

968 

856 

112 

33 

18 

10 

12 

Av. 

6278 

976 

871 

105 

30 

17 

10 

12 

•  Exlra-piilmonary   forms  not   recorded  and  same  proportion  given   as   in   foflowine  decade. 

decade  and  the  same  that  prevailed  forty  years  ago,  before  Koch  discovered 
the  specific  germ  and  fifteen  years  after  \^inemin  had  established  the  con- 
tagious character  of  the  disease.  The  diminution  in  the  deaths  from  tuber- 
culosis has  not  kept  pace  with  that  of  the  general  death  rate. 

Dr.  Schmid,  director  of  the  Swiss  Health  Office  at  Berne,  states  that 
tuberculosis  has  decreased  in  Switzerland  since  the  middle  of  the  eighties. 
This  decrease  is  especially  noticeable  in  the  younger  element  of  the  popula- 

Paac  338 


B.  P.  LYLE 


Table  Shozi'iiitj   Average  Death   Rates  of   Various  Periods  and   Giviiicj   the  Ratio    of 
Deaths  from  Tuberculosis  to  the  General  Death  Rate  and  to  Population 


1870  216,239  4510 

1880  255,139  5653 

1890  296,908  6201 

1900  325,902  5839 


1910 


364,463 


6278 


*576 

534            *42 

812 

753              59 

842 

704            138 

761 

672             89 

976 

871            105 

recorded  aiul  same   proportion   p 

.127  208.6  26.6 

.144  221.9  31.8 

.136  208.8  28.3 

.13  179.1  23.3 


.155 


172.0 


26.8 


tion,  while  it  has  increased  in  those  above  sixty.  The  most  remarkable  de- 
crease has  been  in  children  in  the  first  five  years  of  life.  Out  of  10,000 
there  were  29.0  deaths  in  1901 ;  this  fell  to  18.4  in  1908. 

W'liile  our  records  in  Cincinnati  are  confusing  on  account  of  the  pecu- 
iiarilics  in  nomenclature  or  divergent  views  as  to  the  significance  of  clinical 
conditions,  an  examination  will  show  an  apparent  diminution  of  the  number 
of  deaths  among  children.  They  prove  this  not  only  to  be  true  of  tuber- 
culosis, but  of  other  diseases.  In  1886  the  deaths  among  children  under  five 
years  of  age  constituted  42.86  per  cent,  of  the  entire  mortality  rate;  the  ratio 
for  the  city  being  18.98  per  10,000.  In  1911  the  deaths  in  the  early  years 
of  life  had  been  reduced  to  17.26  per  cent,  of  the  whole,  the  general  mortal- 
ity rate  being  17.23  per  10,000.  This  makes  very  pertinent  the  inquiry:  Does 
not  the  favorable  showing  depend  upon  this  enormous  saving  in  the  lives 
of  children? 

A  close  study  of  these  statistics  will  indicate  that  they  are  more  significant 
than  surface  indications  show.  An  investigation  which  I  made  in  order  to 
estimate  the  comparative  death  losses  of  various  parts  of  the  city  showed 
the  average  loss  per  10,000  to  be  22.5;  in  the  oldest  portion  of  the  city  near 
the  river  it  was  38.0;  the  average  of  the  rest  of  the  basin  and  the  hillsides 
was  22.2;  while  on  the  hilltops  the  rate  was  only  12.5. 

We  must  now  recall  the  fact  that  in  1870  Walnut  Hills  was  the  only 
large  suburb.  It  had  a  comparatively  small  population  which  depended  upon 
omnibu.ses  for  transjiortation.  Ten  years  later  the  same  conditions  prevailed. 
Horse  cars  began  to  go  to  Walnut  Hills  about  1880.  Before  1890  the 
boundaries  of  the  city  were  extended  and  suburban  areas  with  small  death 
losses  from  tuberculosis  were  absorbed.  The  advent  of  the  electric  cars  be- 
fore the  next  decennial  and  the  inclusion  within  the  city  limits  of  large 
suburban  areas  slill  further  enlarged  the  are;is  of  the  city  favorable  for 
residence  purposes. 

Page    ..'.!» 


RAXSOHOFF  MEMORIAL  J'OLUMF 


During  the  past  ten  years  conditions  favoring  a  choice  of  suburban  homes 
liave  improved:  notwithstanding  the  dcatli  rate  from  tuberculosis  has  in- 
creased. 

This  is  possible  because  sanitary  measures,  though  indispensable  and  in- 
valuable, do  not  prevent  infection.  It  will  lie  well  to  consider  this  aspect 
of  the  subject  in  order  that  our  views  on  the  prevention  may  be  made  more 
definite. 

It  seems  somewhat  incomprehensible  that  at  an  almost  legally  established 
time  at  the  conclusion  of  the  body  maturity  a  large  reinfection  or  rather 
recrudescence  of  the  disease  should  occur. 

It  is  not  possible  to  give  a  complete  satisfactory  explanation  of  this, 
although  it  may  not  be  particularly  remarkable  that  at  such  a  period  of  life 
with  such  pronounced  evolutionary  changes  in  the  organism  that  many  slum- 
bering germs  in  the  body  find  conditions  favorable  for  development. 

Hart  believes  that  he  has  found  the  lacking  scientific  explanation,  and 
suggests  that  important  mechanical  incongruities  in  the  region  of  the  upper 
thorax  lead  to  the  causation  of  pulmonary  tuberculosis. 

That  this  view  is  not  generally  accepted  is  shown  by  the  position  of 
Reiche  on  the  heredity  of  chest  conditions  predisposing  to  lung  phthisis, 
and  further  on  the  importance  of  the  habitus  paralyticus  and  its  extent  in 
phthisical  families.  He  thinks  it  will  be  necessary  to  know  whether  it  is  a 
cause  or  an  effect  before  we  can  decide. 

Pottengers'  observations  are  in  striking  contrast  with  the  views  of  Hart 
and  Freund  as  to  the  cause  of  changes  in  the  upper  thorax  cavity  so  fre- 
quently found  in  consumptives.  He  believes  them  to  be  due  to  the  tuber- 
culosis. Williams  years  ago  established  the  fact  that  even  in  early  tuber- 
culosis a  hypertonicity  of  the  muscles  of  the  diaphragm  caused  a  diminished 
movement  upon  the  diseased  side  and  was  an  early  diagnostic  sign.  Pot- 
tenger  holds  that  this  hypertonicity  involves  all  the  muscles  of  respiration 
on  the  involved  side,  particularly  those  of  the  neck.  This  muscle  spasm  dis- 
turbs the  movements  of  the  upper  part  of  the  thorax  causing  a  narrowing 
of  the  intercostal  spaces  and  anchylosis  of  the  costo-sternal  and  manubrio- 
sternal  articulations.  He  also  believes  a  careful  observation  of  the  appear- 
ances of  the  upper  portions  of  the  chest  will  convince  one  that  the  relations 
between  the  tuberculous  lung  involvement  and  these  abnormalities  is  one  of 
cause  and  effect. 

The  doctrine  of  the  importance  of  the  paralytic  thorax  for  the  develop- 
ment of  phthisis,  on  the  one  side,  and  the  theory  of  the  influence  of  early 
infection  as  a  factor  for  the  development  of  consumption  in  adults,  on  the 
other,  are  somewhat  bridged  over  by  these  new  views. 

Pollak,  a  pupil  of  Hamberger,  brings  proof  that  it  is  not  always  true,  as 
has  been  maintained,  that  infection  in  the  first  year  always  causes  death.  He 
shows  that  a  third  of  those  infected  go  over  into  the  second  year  without 
offering  any  prognostically  bad  symptoms.  He  believes  that  infected  infants 
that  do  not  die  of  the  disease  gradually  acquire  a  typical  tuberculous  habitus. 

Page   S'lO 


F.  LYLE 


r-  r-t-f- t^t^t^T^  <«)*«» 'o<o'o<'o» 'o«o*<^o  (s><^c>«^«>  c^t'ooQoottOOOo-i 


Sterblichkeit  an  Lungen&chwind&ucht  auf  je  1000  (m) 

.       -    1000  [w) 
"  (Tuberculose  an-i     »      .    -1000  ^m) 
-   I  derer  Org  a  ne      »     -      -    1000  (w) 
inderStadl    Hamburg    187£-I9ll. 

Table  IX. — Showing  the  reduction  in  mortality  is  not  due  to 
growth  of  the  city,  but  to  the  increase  of  inherent  powers 
of  the  inhabitants. 


RAXSOHOFF  MEMORIAL  VOLUME 


He  maintains  that  the  later  the  infection  occurs  the  less  is  the  liability  for 
clinical  manifestations  and  believes  they  are  seldom  seen  in  children  infected 
after  the  fourth  year.  Whether  this  is  due  to  a  previous  light  infection  or  is 
caused  as  a  physiological  result  of  increased  resistance  he  does  not  state. 
At  any  rate,  these  observations  teach  we  must  recognize  an  immunity  of  the 
growing  organism  toward  outside  infection.  They  also  make  very  improb- 
able the  view  that  consumption  in  the  adult  is  the  result  of  exogenous  infec- 
tion and  support  the  contention  that  the  infection  of  early  years  causes  the 
tuberculous  habitus,  and  therefore  will  be  the  cause  of  the  later  phthisis. 

Roemer  accepts  the  views  of  Pottenger  and  Pollak,  but  still  maintains 
that  the  physical  habitus  can  arise  independent  of  tuberculosis ;  in  his  opinion 
he  is  supported  by  many  observers.  Roemer  believes  observations  should 
be  made  to  ascertain  if  men  clinically  considered  non-tuberculous,  but  with 
typical  paralytic  chests,  will  remain  negative  to  sensitive  tuberculin  tests 
(the  stick  method). 

Conditions  may  be  defined  as  follows : 

If  tuberculous  infection  does  not  cause  rapid  death  it  leads  to  increased 
resistance  against  a  tuberculous  infection. 

The  resistance  so  caused  is  potent  in  preventing  outside  infection  in  later 
years. 

Particular  conditions  of  a  physical  or  jiatliologic  kind  due  to  the  incor- 
poration in  the  body  of  the  tubercle  bacilli  are  such  that  the  degree  of  im- 
munity is  not  sufficient  to  prevent  a  metastatic  reinfection.  Thus  it  occurs 
that  a  new  focus  develops  with  renewed  manifestations  of  tuberculosis. 

Experience  teaches  us  to  view  these  as  metastases  caused  by  a  relatively 
severe  infection  in  childhood. 

A  particularly  disposed  local  condition  for  the  origination  of  this  second 
condition  is  perhaps  in  evidence. 

From  epidemiological  reasons  Hillenberg  opposes  these  views.  In  his  in- 
vestigations on  the  spread  of  tuberculosis  in  a  neighborhood  with  but  slight 
saturation  with  tuberculosis  he  found  a  not  insignificant  number  of  children 
infected.  He  therefore  concludes  that  the  elders  of  these  children  in  their 
youth  must  have  been  proportionately  infected,  and  thinks  it  strange  that  in 
spite  of  this  so  few  or  none  in  later  life  became  consumptives,  although 
when  children  they  were  infected  with  latent  tuberculosis. 

Roemer  directly  opposes  this  view  and  insists  that  the  large  majority  of 
infections  in  children  do  not  result  in  consumption  in  later  life  and  are  never 
noticeable  except  by  the  insensible  protective  influence  against  further  in- 
fection ;  he  further  insists  that  in  those  cases  in  which  consumption  appears 
later  a  particularly  severe  early  infection  occurs.  In  the  territory  investi- 
gated by  Hillenberg  he  thinks  there  was  no  indication  of  serious  early  infec- 
tions, and  the  failure  from  consumption  of  those  only  lightly  infected  in 
childhood  is  not  a  contradiction  of  his  views,  but  a  support  of  their  correct- 
ness. 

Ranke  has  recently  devised  a  very  interesting  chart  tliat  shows  ihe  death 
Page  m 


B.  F.  LYLE 


rate  from  the  recognized  forms  of  the  tuberculosis  of  children  and  adults. 
The  one  being  characterized  by  acute  general  tuberculosis,  the  other  by 
chronic  phthisis.  These  forms  are  seen  in  two  curves.  We  believe  the  for- 
mula correct  which  states  "that  phthisis  is  an  after-disease  of  generalized 
tuberculosis." 

The  increase  of  mortality  from  the  sixteenth  year  on  can  be  caused  theo- 
retically by  increased  facilities  for  infection;  practically  this  in  the  highest 
degree  impossible,  for  phthisis  does  not  immediately  follow  an  opportunity 
for  infection,  but  very  frequently  appears  to  arise  spontaneously  after  inner 
or  outer  general  or  local  injuries. 

Ranke  shows  that  the  phthisis  of  adults  is  the  result  of  the  changes  in- 
augurated by  a  previous  infection.  For  further  proof  he  indicates  the  rarity 
with  which  consumptives  have  the  trachea,  mouth,  fingers,  nose  and  eyes 
involved,  notwithstanding  daily  opportunities   for  infection.     He  mentions 


(^,z% 

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■.::'u\'y< 

m 

I I  =  Itlinisch  gesund  und  nicht  tuberkulinroagierenJ. 

ED  5   klinisch  gesund.  aber  tabeikulinreagierend. 
H  s    tuberkulosekrank. 

Tahle  X. — Diagram   sliowing  the   relative  merit  of   protective   measures   taken   before 
and  after  the  birth  of  the  child. 

again  the  rarity  of  hemostatic  metastases  in  phthisis  in  comparison  with  their 
frequency  in  general  tuberculosis,  although  it  is  proven  that  in  phthisis  the 
tubercle  baccilli  are  frequently  found  in  the  circulation. 

Ranke  proves  further  that  when  secondary  infections  occur  they  are  of 
the  type  of  .superinfections  and  due  to  a  saturation  of  the  blood  with  bacilli 
when  the  resistance  is  low. 

In  the  efforts  to  combat  the  spread  of  tuberculosis  it  must  be  attacked 
from  a  new  viewpoint. 

It  is  shown  by  the  practical  consequences  that  in  the  fight  against  the 
tuberculosis  we  must  either  prevent  the  severer  forms  of  infection,  which  are 


RAXSOHOFF  MEMORIAL  VOLUME 


ultimate  cause  of  the  varities  of  tuberculosis  found  in  adult  life,  or  we  must 
prevent  the  ominous  metastases  in  individuals  infected  in  infancy.  It  is  self- 
evident  that  only  the  assault  of  both  positions  can  be  efificacious.  Because  of 
the  fact  that  tuberculosis  is  a  result  of  infection  early  in  life,  Roemer  is  not 
an  ardent  advocate  of  the  advocacy  of  a  personal  hygiene  that  endeavors  to 
inaugurate  an  efifectual  antagonism  in  adults.  He  believes  this  practice  con- 
trary to  natural  processes  as  is  shown  by  experiments  in  animals. 

In  eliminating  cattle  tuberculosis  no  hygienic  rules  are  efficient ;  only 
methods  that  prevent  infection  show  positive  results. 

The  complete  inefficiency  of  the  hygienic  method  can  not  be  better  illus- 
trated than  by  the  facts  established  by  the  veterinary  service  in  the  Hessian 
district  where,  notwithstanding  extensive  efforts  to  prevent  tuberculous  satu- 
ration the  loss  in  the  majority  of  instances  was  very  considerable,  while  the 
lamentably  appearing  dark  stalls  of  the  small  farmer  were  almost  tubercu- 
losis free. 

In  the  pampas  region  of  Argentina  the  spread  of  tuberculosis  among 
cattle  was  unopposed,  although  they  were  living  under  the  most  favorable 
conditions  in  the  open  air  in  a  sunny  climate,  until  the  owners  concluded  to 
exclude  English  breed  cattle. 

As  long  as  there  is  a  source  of  infection  open-air  conditions  are  useless, 
and  when  calves  are  fed  infected  milk,  as  is  done  in  many  parts  of  Europe, 
the  attempt  to  make  general  hygienic  measures  efficient  are  useless.  While 
isolation  of  consumptives  is  a  relative  isolation  it  is  in  line  with  the  pre- 
vention of  infection. 

The  efforts  to  cure  tuberculous  children  by  means  of  open-air  schools  and 
nourishing  food,  by  means  of  sanatoria  and  isolation  homes,  is  a  duty.  Of 
all  measures  of  prevention  the  protection  of  the  child  is  the  principal  one. 
This  does  not  exclude  other  methods. 

The  effort  must  be  made  to  prevent  severe  childhood  infection.  If  it  is 
known  in  what  families  tuberculosis  is  present  a  great  advance  will  be  made. 
This  may  be  ascertained  by  the  Pirquet  method.  If  the  children  can  then 
be  protected  a  great  problem  will  be  solved.  By  following  out  this  method 
Effler  has  already  attempted  to  judge  the  efficacy  of  this  plan.  While  his 
results  are  few  they  are  remarkable.  With  sixteen  children  born  and  brought 
up  in  families  in  which  before  their  birth  proper  methods  were  counseled 
there  were  at  the  time  of  the  investigation  eight  well  and  not  responsive  to 
tuberculin;  seven  clinically  well  but  reacting;  one  had  pronounced  tubercu- 
losis. This  child  was  from  parents  with  open  tuberculosis,  and.  because 
of  this,  the  measures  of  prevention  could  not  be  thorough. 

Of  nineteen  children  in  which  measures  of  precaution  were  taken  after 
birth  in  open  tuberculous  families,  four  were  healthy  and  non-reacting;  eight 
healthy,  but  reacting;  five  were  tuberculous.  These  figures  are  small,  but 
very  suggestive,  and  indicate  what  is  necessary.  We  know  how  to  protect 
the  children ;  we  possess  means  to  control  the  disease ;  we  must  now  use 
them. 


B.  F.  LYLE 


It  is  first  necessary  to  be  convinced  that  the  secret  of  the  origin  of  con- 
sumption lies  in  early  life,  which  then  becomes  the  field  for  strenuous  effort. 

The  opportunity  to  establish  the  truth  of  these  investigations  lies  in  the 
field  of  the  family  physician.  Upon  him  alone  will  rest  the  responsibility 
for  results.  In  the  accomplishment  of  this  duty  he  will  be  supported  when 
necessary  by  the  strong  and  persuading  influence  of  the  health  department 
and  such  other  organizations  as  earnestly  labor  for  the  eradication  of  the 
tuberculosis  scourge. 


DIZZINESS. 

M.  F.  McCarthy.  ^\.  D.. 

Cincinnati 

L'litil  comparatively  recently  we  lia\e  not  had  at  our  command  the  means 
to  study  and  classify  the  causes  of  dizziness.  Until  the  last  decade  our 
understanding  of  the  mechanism  controlling  balance,  the  disturbances  of 
which  could  result  in  dizziness,  was  very  hazy,  being  made  of  the  uncorre- 
lated  eflforts  of  laboratory  workers  whose  deductions  were  made  for  the  most 
part  from  animal  experimentation. 

In  1825  Flourens  made  excisions  of  portions  of  the  labyrinths  of  animals 
and  noted  that  this  caused  movements  of  the  eyes  and  definite  disturbances 
of  equilibrium.  Purkinje  at  the  same  time  made  experimental  studies  in 
turning  human  beings  and  made  observations  on  the  resulting  ny.stagmus 
and  vertigo.  In  1861  Meniere  published  his  now  famous  case  history  of 
Labyrinthine  Haemorrhage,  verified  by  post-mortem  examinations,  and  by 
his  accurate  observations  established  the  syndrome  known  to  be  typical  of 
the  so-called  ""Meniere's  Disease."  Ewald  and  Hoegyes,  after  years  of  pa- 
tient endeavor  and  research,  were  able  to  state  some  of  the  basic  laws  of 
labyrinthine  physiolog)'.  From  the  observations  of  these  two  men,  together 
with  the  added  experience  of  other  investigators,  Roliert  Barany  was  able 
to  draw  the  material  for  his  magnificent  work  which  has  brought  labyrin- 
thine studies  out  of  what  was  entirely  impractical  state  and  into  the  prac- 
tice of  the  clinics.  His  most  notable  contribution  was  made  in  1913  and 
since  that  time  many  observations,  verified  by  autopsy,  have  brought  this 
work  to  a  degree  of  refinement  in  method  not  hitherto  known. 

Contributions  from  time  to  time  by  workers  in  this  country,  most  notably 
perhaps  Jones  and  Fisher,  of  Philadelphia,  have  brought  us  to  the  realization 
that  there  is  some  clinical  value  to  the.se  tests. 

The  text-book  of  Jones  and  Fisher,  "Equilibrium  and  \'ertig(>."  has  been 
helpful  in  that  it  has  stimulated  interest  in  labyrinthine  studies,  but  has 
gone  far  toward  bringing  all  labyrinthine  .studies  into  question  by  the  wide 
and  sweeping  generalizations  therein  contained.  The  work  of  Griffith,  car- 
ried on  and  published  from  the  psychological  laboratories  of  the  University 
of  Illinois  has  brought  nuich  of  the  work  done  by  Jones  anrl  Fisher,  as  well 
as  the  other  workers  associated  with  the  .\\'iation  Ser\)cr  during  the  war, 
into  question. 

In  as  much  as  the  study  of  dizziness  is  largely  a  study  of  the  mechanism 
which  controls  body  balance,  any  discussion  of  this  subject  must  be  largely  ' 
of  a  physiological  nature.  It  is  the  study  of  a  new  special  sense  which  must 
be  added  to  our  study  of  the  special  senses  of  hearing,  taste,  touch,  smell, 
sight  and  muscle  sense.  This  new  sense  we  must  call  the  kinetic-static  sense, 
or  the  sense  that  appreciates  head  motion  and  head  position,  and  which  thus 
in  a  sense  appreciates  body  motion  and  body  position.     This  sen>e  has  as  its 

Page  SW 


M.  F.  McCarthy 


end  organs  the  labyrinthine  portions  of  the  internal  car,  and  these  end 
organs  have  as  their  sole  function  an  im])ortant  role  in  the  maintenance  of 
balance.  The  term  "end  organ"  is  used  for  the  very  special  purpose  of 
emphasizing  the  fact  that  the  internal  ear  is  an  end  organ  and  nothing  more 
and  that  any  study  of  the  disturbances  of  balance  must  take  into  considera- 
tion not  only  the  end  organ  but  the  nerve  pathways  by  which  its  messages 
reach  the  central  nervous  system.  Also  it  must  deal  with  the  method  of  the 
distribution  of  these  messages  and  their  attendant  reactions,  so  far  as  they 
are  known. 

Perfect  equilibrium  is  maintained  by  the  correlated  activities  of  the  spe- 
cial senses  of  sight,  muscle  sense  and  the  kinetic-static  sense.  Vertigo  can 
be  caused  by  disturbances  of  vision  and  by  a  loss  of  the  proper  ocular  muscle 
balance.  This  type  of  vertigo  is  ordinarily  set  right  at  once  by  properly 
fitted  glasses  and  can  be  recognized  by  the  fact  that  it  is  not  present  when 
the  eyes  are  closed.  Muscle  sense  when  decreased,  absent  or  perverted  may 
decidedly  interfere  with  equilibrium  but  does  not  cause  dizziness.  By  far  the 
largest  number  of  those  complaining  of  the  most  disturbing  symptom  of 
dizziness  are  those  who  have  sustained  some  loss  of  or  irritation  to  the 
kinetic-static  sense  either  in  its  end  organs,  the  labyrinths,  or  to  some  por- 
tion of  their  nerve  pathways. 

As  physicians  we  are  too  often  given  to  loosely  considering  the  ear  as 
an  organ  such  as  the  heart  or  the  liver,  forgetting  that  the  ear  is  only  the 
end  organ  of  two  very  complex  nerve  pathway  systems,  the  one  having  to 
do  with  the  acoustic  function  and  the  other  making  possible  the  knowledge 
of  the  position  and  motion  of  the  head.  In  as  much  as  these  two  sets  of 
fibers  travel  in  the  same  nerve  sheath  as  far  as  the  point  where  they  enter 
the  medulla,  the  tests  of  hearing  are  of  considerable  value  in  giving  some 
idea  of  the  state  of  the  eighth  nerve  at  least  as  far  as  the  point  where  it 
enters  the  medulla.  For  many  years  the  hearing  tests  were  the  only  means 
by  which  the  condition  of  the  vestibular  fibers  might  be  ascertained,  it  being 
reasoned,  with  some  foundation,  that  any  condition  affecting  one  set  of 
fibers,  in  the  same  nerve,  should  aflfect  all  the  other  fibers  in  that  nerve. 

The  difficulty  here  encountered  is  that  later  observation  has  taught  that 
this  is  only  partially  true.  For  some  reason  not  entirely  comprehended, 
the  fibers  having  to  do  with  hearing  are  much  more  sensitive  to  the  actions 
of  toxins  and  much  less  hardy  when  subjected  to  pressure  or  like  injury. 
Under  such  conditions  the  first  fibers  to  cease  to  function  are  the  acoustic 
.ibers,  and  often  we  have  tested  cases  in  which  the  acoustic  function  has 
jeen  completely  lost  but  in  which  the  vestibular  fibers  were  still  functioning. 
The  explanation  offered  for  this  phenomenon  is  that  in  the  scale  of  animal 
development  the  last  functions  to  be  acquired  are  the  least  hardy  and  re- 
sistant to  attack,  the  sense  of  hearing  being  acquired  long  after  the  kinetic- 
static  sense.  However,  the  tests  of  hearing  do  turn  some  light  upon  the 
state  of  the  vestibular  fibers,  but,  what  to  most  of  us  is  more  important,  is 


RANSOM  OFF  MEMORIAL  VOLUME 


that  tests  of  the  vestibular  fibers  give  us  an  insight  into  the  condition  of  the 
acoustic  fibers. 

If  we  are  to  search  for  the  causes  of  dizziness  then  we  must  inquire  into 
the  state,  first,  of  the  labyrinthine  portions  of  the  inner  ears,  and  second, 
their  respective  nerve  pathways.  So  we  are  brought  directly  to  an  inquiry 
into  the  function  of  the  labyrinthine  portions  of  the  inner  ear.  Just  as  the 
child's  first  vision  is  upside  down  and  the  higher  brain  centers  learn  to  in- 
terpret the  inverted  image,  so  when  the  first  head  movement  occurs  and  the 
endolymph  of  the  semi-circular  canal  moves,  the  higher  centers  of  the  brain 
learn  to  associate  that  endolymph  movement  in  one  direction  as  indicative 
of  head  motion  in  the  opposite  direction.  So.  too,  when  the  head  is  rapidly 
turned  from  one  side  to  the  other,  the  higher  centers  in  an  eiTort  to  stabilize 
the  sensorium,  make  the  eyes  lag  behind  a  little  during  the  turn  and  cling 
to  the  objects  as  they  pass.  This  lagging  behind  is  the  slow  component  of 
nystagmus.  As  the  eyes  give  us  some  new  object  to  which  they  are  clinging 
during  the  turn,  they  are  brought  up  with  a  sharp  snap  to  seek  some  new 
object  and  this  is  the  rapid  component  of  nystagmus.  This  explanation,  as 
ofifered  by  Jones,  seems  somewhat  plausible,  and  whatever  explanation  we 
desire  to  accept  w-e  do  know  that  movement  of  the  endolymph  in  one  direc- 
tion in  the  semi-circular  canals  has  become  associated  with  a  slow  eye 
movement  in  the  same  direction  and  a  rapid  eye  movement  in  the  oppo- 
site direction,  the  slow  eye  movement  being  the  direct  result  of  stimula- 
tion from  the  semi-circular  canals.  That  the  higher  centers,  most  prob- 
ably in  the  cerebral  cortex,  are  responsible  for  the  rapid  component  of 
nystagmus  seems  to  be  borne  out  by  the  fact  that  the  rapid  component  is 
not  present  in  induced  general  anaesthesia  or  in  destructive  lesions  of  the 
cerebral  cortex.  A'estibular  irritation,  under  such  conditions,  results  in  eye 
movement  in  the  same  direction  as  the  endolymph  movement,  but  the  rapid 
'component  fails  to  materialize  and  the  eyes  are  deviated  in  this  direction  as 
long  as  the  vestibular  irritation  lasts — conjugate  deviatien. 

Long  years  of  experimental  work  on  the  labyrinths  and  gradual  accumu- 
lation of  clinical  evidence  has  brought  us  to  the  almost  certain  understanding 
that  it  is  through  constant  messages  through  the  semi-circular  canals  that 
balance  of  the  body  is  ordinarily  maintained,  for  it  is  thus  that  the  higher 
centers  realize  head  position  and  head  movement. 

Since  balance  is  in  a  large  measure  dependent  upon  this  knowledge  of 
head  position  and  head  movement,  anything  that  disturbs  the  mechanism 
which  makes  this  knowledge  possible,  disturbs  the  sense  of  balance  or  the 
kinetic-static  sense  and  dizziness  results.  Then,  too,  we  have  come  to  know 
that  the  labyrinths  are  constantly  sending  messages  to  the  nuclei  controlling 
the  eyes  muscles  and  maintaining  for  the  eye  muscles  a  sort  of  tone  or  bal- 
ance. We  know  this  to  be  true  as  any  irritation  to  or  cessation  of  function 
of  either  labyrinth  immediately  results  in  nystagmus,  which  has  a  definite 
direction  and  type  varying  with  the  labyrinth  affected.  For  example:  In- 
jury or  irritation  to  the  right  labyrinth  results  in  a  slow  movement  of  tlie 

Page  .?}8 


M.  P.  McCarthy 


eyes  to  the  right  and  a  rapid  eye  movement  to  the  left,  this  being  known  as 
nystagmus  to  the  left  and  vice  versa. 

Knowing  that  loss  of  function  of  a  labyrinth  or  irritation  to  it  or  its 
associated  pathways  is  accompanied  by  dizziness  or  nystagmus,  or  both,  by 
the  analysis  of  these  two  symptoms  we  have  a  method  of  arriving  at  some 
conclusion  concerning  the  cause  and  its  location.  In  the  analysis  of  dizziness 
one  must  consider  the  direction  and  intensity  of  it  as  manifested  by  the  so- 
called  act  of  past  pointing.  When  the  eyes  are  closed  and  one  is  having  the 
subjective  sensation  of  turning,  if  the  finger  is  put  upon  an  object  and  then 
lifted  into  the  air,  when  the  finger  is  brought  down  to  find  the  object  again, 
instead  of  finding  it  the  finger  points  past  it  to  the  right  or  left,  depending 
upon  the  direction  of  the  subjective  sensation  of  turning.  If  one  feels  that 
he  is  turning  from  right  to  left  he  feels  that  after  having  once  touched  an 
object  and  raised  his  finger  from  it,  that  the  object  has  moved  past  him  to 
the  right,  and  so  when  he  again  attempts  to  find  it  with  his  eyes  closed,  he 
points  past  it  to  the  right,  or,  as  it  has  come  to  be  termed,  past  points  to  the 
right.  Bimanual  past  pointing  as  measured  in  inches  gives  some  indication 
as  to  the  intensity  and  direction  of  the  vertigo.  Since  the  vertigo  has  re- 
sulted from  some  irritation  to  or  destruction  of  the  labyrinths  or  their  path- 
waiys,  past  pointing  gives  some  insight  into  tlie  state  of  these  end  organs  and 
their  fibers,  as  well  as  throwing  some  light  upon  the  nature  of  the  stimulus 
or  lesion  and  its  possible  location. 

Past  pointing  in  itself  is  only  a  small  aid  to  diagnosis  and  to  this  observa- 
tion must  be  added  other  observations  before  even  a  conjecture  is  war- 
ranted. Past  pointing  is  probably  less  important  as  an  observation  than  the 
analysis  of  nystagmus,  for  the  absence  of  nystagmus  after  labyrinthine  irri- 
tation is  always  pathological,  whereas  the  absence  of  past  pointing  may  in- 
dicate a  pathological  condition  or  it  may  not.  However,  presence  of  past 
pointing  in  both  directions  with  both  hands,  elicited  by  the  use  of  the  caloric 
tests,  is  strong  evidence  that  the  cerebellar  hemispheres  are  intact  and  such 
an  observation  certainly  has  its  value. 

It  is  not  the  purpose  of  this  paper  to  attempt  to  cover  the  more  detailed 
portions  of  the  analysis  of  labyrinthine  responses  to  stimulation.  Rather 
it  is  the  purpose  to  discuss  the  basic  principles  of  the  tests  of  labyrinthine 
function  as  brought  out  by  the  efforts  of  many  workers  since  interest  first 
began  in  this  question. 

With  the  head  at  thirty  degrees  forward,  the  plane  of  the  horizontal 
semi-circular  canals  is  parallel  with  the  floor,  and  when  the  body  is  rotated 
with  the  head  in  that  position,  it  is  claimed  the  only  endolymph  movement  is 
in  the  horizontal  canals.  Therefore,  we  know  that  any  resultant  response 
given  in  the  form  of  nystagmus  or  past  pointing  must  come  from  the  endolyph 
movement  in  the  horizontal  canals.  The  greatest  objection  to  the  turning 
tests  is  that  both  labyrinths  are  stimulated  at  the  same  time.  If  the  lesion 
should  be  unilateral  and  not  complete,  the  value  of  the  turning  tests  is  almost 
nothing.    For  reliable  diagnostic  purposes  there  is  only  one  set  of  tests  of  real 


RAXSOHOFF  MEMORIAL  VOLUME 


value  and  these  are  the  so-called  caloric  tests,  in  which  one  ear  at  a  time  is 
douched  with  water  cooled  to  sixtj-eight  degrees  Fahrenheit.  By  this 
method,  by  altering  the  position  of  the  head,  each  set  of  canals  can  be  tested 
separately  and  each  variation  in  the  normal  responses,  in  intensity,  direction 
and  duration  of  nystagmus  and  the  amount  and  direction  of  past  pointing 
be  observed  and  recorded. 

With  the  head  at  thirty  degrees  forward,  the  horizontal  canals  are  parallel 
with  the  plane  of  the  floor,  and  the  plane  of  action  of  the  vertical  canals  is 
at  right  angles  to  the  floor  plane.  When  water  at  a  temperature  of  sixty- 
eight  degrees  Fahrenheit  is  run  into  an  external  auditory  meatus,  with  the 
head  in  this  position,  the  bone  immediately  adjacent  to  the  labyrinth  is  chilled 
and  the  specific  gravity  of  the  endolymph,  rising  at  the  chilled  point,  a  cur- 
rent is  started  downward  toward  the  ampulla  in  the  vertical  canals  only. 
The  fluid  in  the  horizontal  canal  remains  unmoved  as  it  is  parallel  with  the 
plane  of  tlie  floor  and  no  force  of  gravity  is  in  action  on  its  endolymph. 
r.y  varying  the  position  of  the  head  from  thirty  degrees  forward  to  sixty 
degrees  Imckward,  we  place  the  plane  of  action  of  the  vertical  canals  parallel 
with  the  floor  and  now  the  horizontal  canals  are  at  right  angles  to  the  floor 
plane.  At  once  the  endolymph  of  the  vertical  canals  comes  to  rest  and  the 
current,  if  it  is  such,  begins  to  move  downward  away  from  the  ampulla  in 
the  horizontal  canal.  By  this  means  we  are  able  to  test  each  set  of  canals 
separately  without  having  to  resort  to  head  motion  to  set  up  our  endolymph 
currents,  the  same  responses  being  given  in  past  pointing  and  nystagmus  a; 
though  head  motion  had  occurred  in  a  direction  opposite  to  the  direction  of 
the  endolypmh  current  or  flow.  \\'hile  variations  do  occur  in  cases  where, 
due  to  drum  thickening  or  bone  changes,  the  chilling  of  the  canals  is  de- 
layed, the  average  patient,  following  douching  of  an  ear  with  water  at  a 
temperature  of  sixty-eight  degrees  Fahrenheit,  will  exhibit  the  ocular  move- 
ments characteristic  of  nystagmus  in  from  forty  to  sixty  seconds  from  the 
time  the  douching  is  begun.  Forty  seconds  was  the  titne  as  set  by  Jones  in 
his  review  of  many  thousand  tests  made  on  aviators  during  the  war.  How- 
ever, our  tests  on  the  average  clinical  patient  have  shown  that  this  figure 
is  a  little  low  and  that  it  is  more  apt  to  be  fifty  to  sixty  than  it  is  forty,  and 
often  may  run  over,  that  in  cases  that  do  not  exhibit  any  marked  drum 
changes.  Some  of  these  patients  have  been  douched  several  times  with  the 
same  results  and  have  been  followed  for  over  a  year  without  exhibiting  the 
slightest  suggestion  of  any  pathological  changes  in  either  the  acoustic  func- 
tion or  the  kinetic-static  sense.  However,  the  thousands  of  tests  being  done 
and  to  be  done  in  the  future  will  settle  such  questions  very  definitely  within 
the  next  decade. 

If  the  douching  of  an  ear  is  continued  until  the  ocular  movements  reach 
a  maximum,  there  should  be  present  past  pointing  with  both  hands  in  the 
same  direction  to  the  side  of  the  ear  stimulated.  This  past  pointing  may 
vary  somewhat  in  amount,  the  reaction  being  somewhat  mure  marked  in 
some  people.     Since  this  past   pointing  is  in  a  sense  an   indication  of   the 

Page  SSO 


M.  F.  McCarthy 


amount  of  dizziness,  we  ordinarily  expect  it  to  be  present  in  continuous 
and  well-defined  vertigo.  Providing  there  is  not  some  lesion  of  the  lobes 
of  the  cerebellum  which  will  interfere  with  the  synergy  of  the  arms  as  the 
eli'ort  is  made  which  results  in  inward  or  outward  pointing  of  the  arms,  this 
past  jiointing  should  be  bilateral. 

When  we  remember  that  in  the  caloric  tests,  done  by  douching  the  ears, 
we  are  testing  each  set  of  canals  separately,  as  well  as  their  associated  nerve 
pathways,  the  significance  of  the  tests  becomes  apparent.  In  the  last  few 
years  it  has  become  fairly  well  established  that  the  fibers  from  the  vertical 
and  horizontal  canals  do  not  follow  the  same  paths  after  the  fibers  of  the 
eighth  nerve  have  entered  the  upper  portion  of  the  medulla.  The  paths 
they  pursue,  as  at  present  understood  and  upon  which  understanding  suc- 
cessful localizations  are  being  made,  is  that  the  fibers  from  the  horizontal 
canals  dip  down  into  the  medulla  and  end  in  Dieter's  muclei.  From  there, 
fibers  pass  to  the  posterior  ground  bundles  which  join  up  the  nuclei  of  the 
nerves  controlling  the  eye  movements  exhibited  during  nystagmus.  The 
greater  part  of  the  remaining  fibers  pass  into  the  inferior  cerebellar  peduncles 
of  their  respective  sides  and  so  reach  the  cerebellar  nuclei. 

On  the  other  hand,  immediately  upon  entering  the  upper  portion  of  the 
medulla,  the  fibers  from  the  vertical  canals  pass  upward  and  enter  the  pons, 
where  they  terminate  in  some  homolateral  nuclei  as  yet  not  certainly  known. 
These  nuclei  are  also  linked  up  to  the  pontine  nuclei  controlling  the  eye 
movements,  by  fibers  which  pass  to  the  posterior  ground  bundles.  The 
greater  part  of  the  remaining  fibers  reach  the  cerebellar  nuclei  by  way  of 
the  middle  cerebellar  peduncles  of  the  same  side. 

Hence,  it  is  said  by  testing  the  horizontal  canals  we  are  testing  not  only 
the  integrity  of  the  canals  themselves,  but  the  integrity  of  the  upper  portion 
of  the  medulla,  the  inferior  cerebellar  ])eduncles,  and  the  homolateral  cerebel- 
lar nuclei.  So,  too,  by  testing  the  vertical  canals  of  one  side,  we  test  also  the 
integrity  of  the  lower  and  lower  middle  portions  of  the  pons,  the  middle 
cerebellar  jjeduncle  and  the  cerebellar  nuclei  of  the  same  side.  Since  it  is 
by  means  of  the  superior  cerebellar  peduncles  that  the  cerebellar  nuclei  are 
joined  to  the  higher  centers  in  the  cerebral  cortex,  where  take  place  the 
complex  associations  of  stimuli  necessary  for  the  knowdedge  of  motion  of 
the  head  or  of  its  position  in  space,  we  are  given  some  information  concern- 
ing the  state  of  the  tracts  of  the  superior  cerebellar  peduncles  themselves. 
Since  with  our  tests  we  are  given  some  information  concerning  the  activi- 
ties of  the  fibers  traversing  such  important  structures  as  the  medulla,  pons, 
the  cerebellar  peduncles  and  hemispheres,  as  well  as  the  higher  cerebral 
centers  from  which  originate  the  arm  movements  having  to  do  with  past 
pointing,  their  importance  warrants  consideration.  Nor  is  this  importance 
lessened  by  the  fact  that  in  some  measure  the  condition  of  each  of  these 
structures  can  be  estimated  separalelx-. 

(  )ur  interest  in  this  work  has  come  nut  from  ;iny  desire  to  enter  upon  a 
career  in  neuro-otology,  but   rather   from  a  desire  to  find  some  means   of 


RAXSOHOFF  MEMORIAL  VOLUME 


throwing  light  upon  the  condition  of  the  internal  ears  in  all  too  numerous 
cases  of  hopeless  deafness  that  have  come  into  our  hands.  Then,  too,  we 
have  been  seeing  more  and  more  patients  complaining  of  dizziness  in  which 
we  felt  the  integrity  of  the  internal  ears  was  established.  Since  no  examina- 
tion of  the  internal  ear  can  be  complete  without  having  considered  the  state 
of  its  nerve  tracts  as  well,  there  is  no  choice  for  the  otologist  who  is  con- 
fronted with  the  necessity  of  attempting  to  find  the  cause  or  causes  or  re- 
current dizziness  in  one  of  his  patients.  All  the  light  that  neurologists,  with 
whose  collaboration  this  work  should  always  be  done,  can  throw  together 
with  that  of  otological  observation,  is  only  too  often  too  feeble  to  allow  us 
to  see  clearly  to  the  cause  and  so  be  guided  to  the  relief  of  the  suffering 
patient. 

There  is  no  doubt  that  most  of  the  cases  of  dizziness  which  we  see  are 
due  to  affection  of  the  internal  ears  or  their  immediately  adjacent  nerve 
supply.  The  difficulty  may  be  occasioned  by  some  disturbance  of  the  blood 
supply  to  the  parts,  anaemia  or  hyperaemia,  or  to  the  presence  of  some  toxic 
material  which  has  reached  these  structures  either  through  the  blood  or 
lymph  chanels  or  by  the  simple  diffusion  or  toxic  material  through  the  bone, 
as  can  happen  in  purulent  infection  of  the  middle  ear.  These  cases,  once 
the  toxic  material  is  eliminated  or  the  circulatory  disturbances  set  right 
or  the  middle  ear  drained  of  the  pus,  promptly  recover.  However,  we  must 
be  constantly  on  our  guard  for  the  cases  of  persistent  dizziness  or  for  those 
cases  which  recur  at  frequent  intervals  and  in  which  there  is  some  question 
as  to  whether  means  taken  to  combat  the  cause  is  being  effective  or  not. 
We  must  not  forget  that  it  may  not  have  been  our  remedial  measures  which 
re.sulted  in  the  cessation  of  dizziness,  but  that  it  may  simply  mean  a  cessation 
in  the  amount  of  local  or  general  nerve  pressure.  Nothing  is  more  perplex- 
ing than,  in  cases  of  known  central  lesion  accompanied  by  a  rise  of  intra- 
cranial pressure,  to  find  that  one  day  a  set  of  fibers  are  working  and  the 
next  day  to  find  their  function  totally  lost,  to  be  in  turn  followed  by  almost 
complete  recovery  of  function  within  the  following  twenty-four  hours.  In- 
tracranial pressure  as  manifested  by  inhibition  of  nerve  action  is  certainly 
an  extremely  variable  quantify  and  marked  and  prolonged  remissions  of 
symptoms  are  often  found  in  even  the  most  serious  of  intracranial  lesions. 
It  is  these  remissions  which  lull  us  so  often  into  a  false  sense  of  security  in 
the  early  observation  of  patients  complaining  of  dizziness  and  the  patient 
is  dismissed  from  observation  as  having  been  the  victim  of  some  unknown 
type  of  toxaemia  which  has  passed  away. 

We  must  remember  that  dizziness  can  result  from  any  disturbance  to 
function  of  the  semi-circular  canals  or  of  their  nerve  pathways  to  the  cere- 
bral cortex.  The  stomach  itself  is  not  the  cause  of  dizziness  except  as  a 
hyperacidity  may  influence  the  (|uanlity  or  quality  of  the  blood  supplied  to 
these  parts,  h'ocal  infectinn  from  leedi  or  tonsils,  constipation,  diabetes, 
nephritis,  tumor  masses,  and  so  forth,  only  cause  dizziness  as  they  destroy 
parts  of  or  upset  the  workings  of  these  balance  control  systems. 


M.  f.  McCarthy 


Every  disturbance  of  these  systems  is  immediately  attended  by  dizziness 
or  nystagmus,  or  both.  If  complete  destruction  of  one  of  these  balance  con- 
trol systems  has  taken  place,  as  may  occur  in  the  destruction  of  the  internal 
ear  of  one  side  or  the  complete  degeneration  of  an  eighth  nerve,  this  dizziness 
may  persist  in  the  most  severe  form  for  weeks,  attended  by  an  almost  con- 
stant ny,stagmus  of  a  type  that  varies  in  its  nature  according  to  the  ear  or 
nerve  afifected. 

Gradually,  in  this  form  of  disturbance  to  the  kinetic-static  sense,  the  re- 
maining system  takes  up  in  part  the  function  of  the  one  lost  and  the  higher 
centers  learn  either  to  ignore  the  disturbing  stimuli  coming  in  over  nerve 
pathways  from  the  destroyed  area  or  to  rely  upon  the  remaining  system  re- 
enforced  by  the  knolvledge  of  the  body's  position  in  space  by  the  muscle 
and  visual  senses.  The  past  pointing  and  nystagmus  present  in  such  dis- 
turbances, resulting  as  they  do  from  some  stimulus  or  lack  of  stimulus 
from  within,  are  termed  spontaneous  past  pointing  and  spontaneous  nystag- 
mus to  differentiate  this  type  from  that  resulting  from  external ^imuli,  such 
as  are  used  in  the  caloric  and  turning  tests. 

There  are  two  types  of  spontaneous  nystagmus  to  be  observed — the 
rhythmic,  in  which  it  is  possible  to  distinguish  a  slow  movement  in  one 
direction  associated  with  a  rapid  movement  in  the  opposite,  and  the  os- 
cillating type,  in  which  both  movements  are  of  equal  rapidity.  Tlie  oscil- 
lating type  has  no  relationship  whatever  with  the  disturbances  of  the  kinetic- 
static  sense,  and  is  due  entirely  to  either  an  early  acquired  or  con- 
genital central  visual  defect.  This  type  of  nystagmus  becomes  much  more 
marked  whenever  visual  fixation  is  attempted  and  can  be  differentiated  with 
relative  ease  from  the  rhythmic.  Close  observation  of  the  rhythmic  type  will 
disclose  to  which  side  the  rapid  movement  or  component  is  taking  place,  and 
if,  for  example,  it  is  to  the  right,  then  the  nystagmus  is  said  to  be  to  the 
right.  Rhythmic  nystagmus  resulting  from  the  complete  cessation  of  func- 
tion of  one  or  the  other  of  the  balance  control  systems,  has  a  mixed  rotary 
and  horizontal  movement  to  the  slow  component.  When  it  results  from  a 
disturbance  to  the  vertical  canals  or  their  nerve  supply  alone,  the  nystagmus 
has  a  rotary  element  alone  as  its  slow  com])onent.  When,  however,  the  dis- 
turbance affects  the  horizontal  canals  or  their  related  nerve  supply,  the  slow 
component  is  entirely  horizontal.  So  it  is  that  the  analysis  of  spontaneous 
rhythmic  nystagmus  gives  us  often  very  important  clues  as  to  the  type  and 
location  of  the  disturbance  in  function  that  is  resulting  in  dizziness  to  the 
patient.  Spontaneous  rhythmic  nystagmus  upward  or  downward  is  prac- 
tically always  indicative  of  pontine  pressure. 

The  difficulties  attending  constructive  work  in  this  field  are  manifold. 
Cases  of  this  type  progress  so  slowly  that  many  observations  made  on  those 
who  are  in  the  early  stage  of  the  development  of  their  lesions  are  never 
followed  by  later  observations.  In  a  semi-invalid  state  they  drift  from  ono 
])hysician  to  another  and  often  are  completely  lost  for  the  opportunity  of 
further  study.    This  work  is  still  in  the  active  phase  of  discovery  and  prog- 

Pagc  .X),; 


RANSOHOFF  MEMORIAL  VOLUME 


ress  and  nnich  will  be  adderl  in  the  future  which  will  be  of  great  benefit  to 
humanity.  I  have  no  desire  to  paint  the  picture  in  too  glowing  terms,  for 
the  diagnosis  of  many  of  these  conditions  is  a  matter  of  prolonged  and 
painstaking  observation.  In  many,  many  cases  we  fail  to  make  a  diagnosis 
due  to  obstacles  which  we  have  not  yet  been  able  to  overcome.  There  is  no 
doubt  that  the  tests  have  been  overrated  by  some  over-enthusiastic  workers 
who,  in  a  measure,  have  brought  the  tests  into  a  certain  amount  of  disrepute. 
There  is  no  doubt,  however,  that  this  work  has  its  very  positive  field  of 
usefulness  and  that  the  future  will  see  much  added  in  the  improvement  of 
technique  and  a  widening  of  its  breadth  of  service. 

I  wish  to  take  this  opportunity  to  thank  Dr.  Louis  Fisher,  of  Philadel- 
phia, for  his  kindness  in  allowing  me  the  privilege  cff  reviewing  his  case 
records.  I  wish  also  to  express  my  appreciation  for  the  kindness  of  Dr. 
Bentley  and  Dr.  Coleman  Griffith,  of  the  Psychological  Department  of  the 
University  of  Illinois.  I  wish  to  express  my  admiration  for  the  accurate  and 
monumentarwork  being  carried  on  in  their  laboratories  for  the  purpose  of 
advancing  our  knowledge  of  labyrinthine  physiology. 


THE  PINEAL  GLAND.* 

THE  PINEAL  GLAND'S  LNFLUENCE  UPON  GROWTH  AND  DIFFERENTL'\- 

TION   WITH   PARTICULAR   REFERENCE  TO   ITS   INFLUENCE 

UPON   PRENATAL  DEVELOPMENT. 

Carey  Pratt  McCord,  M.  D., 

Detroit. 

L     L\TUODUCTIO.\" 
(A  cursory  review  of   recent   work   pertinent   to   pineal    functioning.) 

The  evidences  that  hnk  the  pineal  body  with  a  glandnlar  function  are 
much  less  definite  than  for  such  glandular  organs  as  the  thyroid,  hypo- 
physis, ovary,  and  the  suprarenals.  Doubt  is  frequently  expressed  that  the 
pineal  body  is  more  than  a  functionless  vestige  of  what  was  once,  in  earlier 
evolutional  stages,  a  functioning  eye.  Other  observations  have  led  to  the 
contention  that  the  pineal,  through  metamorphosis,  has  become  a  highly  spe- 
cialized tissue  that  serves  the  body  in  a  manner  coinparable  with  the  major 
members  of  the  endocrinous  system. 

The  purpose  of  the  present  paper  is  to  group  the  essential  findings  from 
the  recent  literature  into  a  concise,  unbiased  resume,  adequately  expressing 
the  status  of  the  pineal  body  as  a  functioning  organ.  To  this  are  added  the 
writer's  more  recent  observations  upon  the  growth  of  young  animals  under 
the  influence  of  pineal  materials. 

ANATOMY  AND  EMBRYOLOGY 
(Bibliography  numbers   1-57) 

The  pineal  body  (pineal  gland,  epiphysis,  conarium)  is  situated  in  the 
brain  just  beneath  the  splenium  of  the  corpus  callosum.  (Fig.  1.)  It  lies 
suspended  between  the  anterior  quadrigeminate  bodies.  The  gland  is  con- 
sequently just  above  the  Sylvian  aqueduct.  The  internal  cerebral  veins  lie 
above  and  partially  encircle  the  pineal.  In  the  human  the  pineal  is  nearly 
trilateral  in  shape,  in  sheep  is  round,  in  cattle  is  oval.  The  average  weight  in 
cattle  is  .2  grams  and  in  sheep  .13  grams.  Primarily  the  pineal  is  developed 
as  a  thin  ependymal  diverticulum  from  the  diencephalon,  extending  between 
the  posterior  and  habenular  commissures.  At  a  later  stage  this  diverticulum 
thickens  and  encloses  some  of  the  adjacent  vascular  mesoderm  to  form  the 
mature  organ.     (Streeter.) 

In  those  publications  cited  in  the  bibliography  as  pertinent  to  the  anat- 
omy, embryology,  and  histology  of  the  pineal,  the  studies  have,  for  the  most 
part,  been  prosecuted  toward  establishing  (1)  the  presence  of  glandular 
tissue;  (2)  the  presence  of  contractile  tissue  supporting  the  view  that  the 
gland  is  a  valve  regulating  the  flow  of  cerebrospinal  fluid;  (3)  nerve  fiber 
communication  between  this  gland  and  other  parts  of  the  brain;  (4)  evi- 
dence of  involution  changes  in  the  gland  indicating  a  cessation  of  function. 

•  From  the  Transactions  of  the  American  Gynecological  Society,   1917 


RAX  son  OFF  MFMORIAL  I'OLUMF 


These  ])ul)licatinns  may  be  summarized  as  indicating:  (1)  Complete 
cytologic  studies  in  several  species  allow  the  inference  that  the  pineal  body 
is  glandular  in  nature.  The  glandular  elements,  however,  are  few  and  illy 
defined.  (2)  The  occasionally  demonstrated  muscle  fibers  in  the  pineal  are 
without  significance  to  pineal  function.  (3)  Nerve  fibers  and  neuroglia  arc 
to  be  found  at  least  in  certain  animals,  but  these  are  probably  of  trivial 
import.  (4)  The  gland  undergoes  involution  changes,  beginniug  in  the 
human  as  early  as  the  seventh  year.  Involution  is  pronounced  at  puberty. 
The  degeneration  is,  however,  not  complete  and  the  histologic  picture  of  the 
adult  gland  is  not  such  as  to  remove  the  ]:)ossibility  of  a  continued  function 
in  adult   life. 

PIXEAL   XHt)Pr,.\SMS    .\.\D    KESULTIXG   FUXCTIOX.XI,    i:)lSTUI^B.\XCES 
(  Bililiography    numbers    100-189) 

Tumors  of  the  pineal  are  not  of  frecjuent  occurrence.  Tlic  total  num- 
ber of  authentic  cases,  with  subsecjuent  necrojisy  findings  in  some,  is  not 
more  than  seventy.  These  cases  have  been  the  source  of  the  greatest  infor- 
mation as  to  the  functions  of  the  pineal.  In  1898,  Heubner  described  a  boy 
of  foiu-  and  one-half  years  who  showecl  a  precocious  sexual  and  somatic 
growth.  The  body  of  this  boy  was  that  of  a  boy  of  eight  or  nine  years.  The 
genitalia  corresponded  to  the  proportions  found  at  puberty.  The  pubic  hair 
was  1  cm.  long.  A  year  later  at  autopsy  a  teratoma  of  the  pineal  was  dem- 
onstrated. By  1907,  Marburg  was  able  to  collect  fort\-  histories  of  such 
types.  He  sought  to  establish  a  clinical  entity  for  pineal  dysfunction.  The 
term  "Macrogenitosomia  prfecox"  has  subse(|uently  designated  this  condi- 
tion. In  a  more  recent  paper.  Marburg  attributes  to  the  condition  tlie 
following  characteristics : 

1.  General.  These  include  all  the  usual  signs  of  intracranial  pressure, 
usually  secondary  to  a  subsequent  internal  hydrocephalus. 

2.  Neighborhood.  These  for  the  most  part  are  dependent  upon  en- 
croachment upon  the  quadrigeminate  bodies,  leading  to  diverse  oculomotor 
paralyses  and  pupillary  disturbances,  and  encroachment  upon  the  cere- 
bellum, with  ataxic  manifestations. 

3.  Constitutional.  Under  this  designation  are  grouped  tiie  manifesta- 
tions attributable  to  the  derangement  of  the  pineal  glandular  function.  This 
constitutional  syndrome  consists  of  first,  early  sexual  maturity,  evidenced  in 
the  enlarged  sex  organs,  pubic  hair,  general  body  hair,  early  change  in  voice  ; 
second,  precocious  mental  development,  evidenced  in  the  maturity  of  thought 
and  speech ;  third,  general  body  overgrowth  to  the  extent  that  a  child  of 
five  or  six  years  may  have  the  appearance  of  a  child  of  eleven  or  twelve. 

Frankl-Hochwart  similarly  has  summed  up  the  characteristics  of  this 
pathologic  state.  He  states.  "When  one  finds  in  a  very  young  individual, 
along  with  the  general  sympionis  of  tumor  as  well  as  the  signs  of  a  lesion 
of  the  cor])ora  quadrigemina.  alinorm.-il  body  growlli,  unusual  growth  of 
Hasir  :!r.i: 


CAREY  PRATT  McCORD 


hair,  adiposity,  somnolence,  ]ireniature  genital  and  sexual  development,  and 
finally  intellectual  maturity,  one  must  think  of  pineal  tumor." 

Of  the  seventy  cases  at  the  present  time  available  in  the  literature,  only 
twenty-five  occurred  prior  to  puberty.  Because  of  the  pineal  involution 
that  occurs  by  the  time  of  puberty,  only  in  these  twenty-five  cases  are  consti- 
tutional manifestations  to  be  anticipated.  It  is  significant  that  with  two 
exceptions  all  cases  occurred  in  boys. 

Many  cases  of  pineal  tumors  before  puberty  manifest  none  of  the  signs 
of  precocity  of  development  that  are  so  striking  in  a  few  selected  cases.  A 
study  of  the  clinical  material  reveals  how  little  consideration  has  been  given 
to  the  possibility  of  pluriglandular  involvement.     In  fact,  some  early  cases 


Fig.   1— Sagittal   section  of  htef 


showing   size,   position,   and    relation   of    pineal 
gland. 


the  necropsy  demonstration  of  a  pineal  tumor  led  to  the  association  of  all 
prior  metabolic  changes  to  pineal  functional  perversion.  This  grew  out  of 
the  prevalent  conception  of  each  endocrine  gland  as  an  entity  entering  into 
no  interrelations  with  other  similar  organs.  Judging  these  cases  in  the 
light  of  recent  advances  in  pituitary  pathology  and  physiology,  it  is  difficult 
to  delineate  the  manifestations  of  pure  pineal  derangement  from  a  pluri- 
glandular condition.  Gushing  has  pointed  out  that  from  the  intracranial 
alterations  attending  pineal  neoplasms,  the  hypophyseal  functions  are  read- 
ily deflected  from  the  normal. 

This  infrequent  condition  in  which  the  growth  and  dififerentiation  into 
the  adult  is  so'  deviated  from  the  normal  that  very  young  children  acquire 

ratic  r,7 


RAN  son  OFF  MFMORIAL  VOLUME 


in  part  the  sexual,  mental  and  somatic  characteristics  of  maturity,  has  nat- 
urally led  to  diverse  attempts  to  induce  such  a  condition  experimentally. 
Through  the  extirpation  of  the  pineal,  through  the  feeding  of  pineal  sub- 
stances to  young  animals,  through  the  intravenous  and  subcutaneous  admin- 
istrations of  pineal  extracts,  has  information  been  sought  as  to  the  signifi- 
cance of  this  organ  in  the  body's  economy.  The  outcome  of  such  investiga- 
tions are  described  in  subsequent  paragraphs. 

EXTIRPATION'  OF  THE  PINEAL  GLAND 
(Bibliography  numbers  71-78) 

Situated  near  the  center  of  the  brain,  the  inaccessibility  of  the  pineal 
has  prevented  any  widespread  use  of  this  method.  The  trauma  is  neces- 
sarily severe  and  until  the  recent  reports  by  Dandy  (1915)  and  Horrax 
(1916)  the  mortality  has  been  very  high — seventy-five  deaths  out  of  ninety- 
five  operations  in  one  series,  and  twelve  deaths  out  of  fifteen  operations  in 
another.  With  so  high  a  mortality  it  may  be  questioned  whether  the  few- 
survivors  would  exhibit  constant  changes  referable  to  pineal  deprivation. 
The  mortality  is  usually  due  to  hemorrhage  into  the  ventricle  from  injury 
to  the  central  cerebral  veins,  or  to  direct  injury  to  the  quadrigeminate  bodies 
or  adjacent  brain  tissues.  Dandy  has  recently  developed  an  operative  pro- 
cedure whereby  much  of  the  trauma  is  obviated.  The  essential  innovation 
lies  in  an  approach  through  section  of  the  splenium  of  the  corpus  callosum 
thus  permitting  freer  manipulations  in  the  operating  field.  Although  the 
mortality  may  thus  be  reduced,  the  results  obtained  by  Dandy,  on  com- 
parison with  those  obtained  more  recently  by  Horrax,  are  uniformly  dis- 
similar. The  respective  summaries  of  these  two  investigators  quoted  below 
indicate  how  incomplete  are  our  available  data  bearing  upon  extirpation  as 
a  method  of  approach  to  the  problems  of  pineal  function.    Dandy  states : 

"1.  Following  the  removal  of  the  pineal  I  have  observed  no  sexual  precocity  or 
indolence,  no  adiposity  or  emaciation,  no  somatic  or  mental  precocity  or  retardation. 

"2.  Our  experiments  seem  to  yield  nothing  to  sustain  the  view  that  the  pineal 
gland  has  any  active  endocrine  function  of  importance  either  in  the  very  young  or 
adult  dogs. 

"3.  The  pineal  is  apparently  not  essential  to  life  and  seems  to  have  no  influence 
upon  the  animal's  well-being." 

These  negative  findings  are  in  keeping  with  the  earlier  work  of  Exner 
and  Boese,  and  Biedl.  Subsequent  to  Dandy's  publication  an  extended  report 
has  been  made  by  Horrax,  whose  positive  findings  are  in  keeping  with  those 
of  Foa  and  Sarteschi.    Horrax  states: 

"L    Total   experimental   pinealectomy   is   possible   in  guinea-pigs   and   rats. 

"2.  Pinealectomized  made  guinea-pigs  show  a  hastened  development  of  the  sexual 
organs,  manifested  before  maturity  by  a  relative  increase  in  size  and  weight,  both  of 
the  testes  and  seminal  vesicles,  over  control  pigs  of  the  same  litter. 

"3.  Histologically  the  testes  and  seminal  vesicles  of  these  animals,  if  taken  before 
the  age  of  sexual  maturity,  show  a  more  advanced  physiological  state  than  their  con- 
trols. 

"4.  The  pinealectomized  females  appear  to  show  a  tendency  to  breed  earlier  than 
controls  of  the  same  age  and  weight. 

Page  35S 


CAREY  PRATT  McCORD 


"5.  For  several  reasons,  young  rats  are  likely  to  prove  better  subjects  for  experi- 
mental pinealectomy  than  young  guinea-pigs,  and  some  evidence  of  hastened  maturity 
has  been  obtained  in  this  species." 

IMMEDIATE   RESULTS    FOLLOWING    THE    INTRAVENOUS    OR    SUBCU- 
TANEOUS  ADMINISTRATION    OF    PINEAL  EXTRACTS 
(Bibliography  numbers  58-70) 

Unlike  the  intense  cardio-vascular  action  of  suprarenal  extracts,  or  the 
uterine  contracting  action  of  pituitary  extracts,  the  immediate  results  from 
intravenous  or  hypodermic  injections  of  pineal  extracts  are  not  pronounced. 


Fig.  2. — /\  comparison  of  the  effect  on  surviving  guinea-pig  uterus  of  pituitary 
and  pineal-gland  extracts.  The  height  of  contraction  from  the  pineal  extract  admin- 
istered at  B  is  trivial  in  comparison  with  the  contraction  at  A  induced  by  the  much 
smaller  quantity  of  pituitary  extract.     Time  in  minutes. 

Such  phenomena  as  decrease  in  arterial  tension,  dilatation  of  the  blood  ves- 
sels, altered  amplitude  and  rate  of  the  heart  beat,  diuresis,  glycosuria,  and 
uterine  contractions  have  been  reported  and  confirmed.  Under  experimen- 
tal conditions  the  contraction  produced  in  the  uterus  by  1  cc.  of  20  per  cent, 
pineal  extract  is  much  less  intense  than  the  contraction  produced  by  1/200 
cc.  of  20  per  cent,  pituitary  extract.  (Fig.  2.)  The  intensity  of  these  sev- 
eral activities  is  so  slight  that  at  the  present  time  only  technical  importance 
may  be  attached  to  these  findings. 


FEEDING    EXPERIMENTS    WITH    PINEAL    GLANDS 
(Bibliography   numbers   79-87) 

The  syndrome  of  precocious  development  seen  in  the  human  is  usually 
interpreted  as  the  outgrowth  of  pineal  deficiency — a  hypopinealisni.  Such 
being  the  case,  if  the  feeding  of  pineal  materials  determined  any  changes, 
a  state  just  opposite  that  cited  above  would  be  anticipated — a  condition  of 
deferred  sexual,  mental  and  somatic  maturity.  Curious  to  record,  feeding 
experiments  lead  to  rapid  sexual  and  somatic  development. 

Dana  and  Berkeley  fed  pineal  materials  to  young  animals  (kittens,  rabbits,  guinea- 
pigs),  and  noted  a  25  per  cent,  excess  in  weight  over  controls.  These  investigators 
sought  to  determine  the  extent  of  stimulating  influence  upon  children  of  low  mentality. 
Fifty  feeble-minded  children  were  treated  and  suitably  controlled  with  other  children 
of  the  same  age  and  diagnosis.  Binet  tests  were  the  criteria  of  mental  advancement. 
No  physical  changes  resulted  but  on  prolonged  treatment  the  mental  development 
was  greater  than  that  prior  to  treatment  and  in  excess  of  control  children  of  the  same 

Page  !i.W 


RANSOHOFF  MEMORIAL  VOLUME 


mental  age.  These  studies  on  feehlc-niinded  children  afford  certain  technical  evidences 
of  value  but  the  quantity  of  improvement  resulting  is  not  sufficient  to  warrant  any 
widespread  use  of  pineal  materials  as  a  profitable  treatment  of  feeble-mindedness. 

Hoskins  (1916)  in  feeding  experiments  upon  albino  rats,  studied  the  inHuence  upon 
the  growth  of  the  various  ductless  glands  including  thyroid,  thymus,  hypophysis,  and 
pineal.  His  results  would  indicate  that  none  of  these  glands  have  any  constant  effect 
upon  the  growth-rate  of  young  rats. 

McCord  (1914,  1915)  employed  400  young  animals  (chickens,  guinea-pigs,  dogs) 
in  experiments  to  establish  the  extent  of  influence  the  pineal  exerts  upon  growth  and 
development.  He  concludes  from  his  experiments  that  the  same  precocity  of  develop- 
ment usually  attributed  to  pineal  deficiency  (hypopinealism)  was  obtained  in  animals 
by  supplying  an  increased  amount  of  pineal  substance  by  feeding  or  injecting  pineal 
preparations.  Such  administration  of  pineal  substances  led  to  a  more  rapid  growth  of 
body  than  normal,  and  determined  an  early  sexual  maturity.  The  excess  in  rate  of 
growth  was  most  pronounced  (40.9  per  cent,  excess  in  eleven  weeks)  in  young  animals 
fed  with  pineal  tissue  obtained  from  young  animals,  Xo  tendency  to  gigantism  has 
followed  pineal  administration.  After  maximum  size  was  attained,  pineal  administra- 
tion appeared  to  be  inefi'ective.  Both  males  and  females  respond  to  the  influence  of 
pineal  substances  in  rate  of  growth,  but  the  response  has  been  more  definitely  mani- 
fested in  males. 

II.    THI-:   PIXR.M,  C.L.AND'S   INFLUENCE  UPON   GROWTH   .AND 
DIFFERENTI.ATION 

(.\    record   of   experiments   upon   postnatal   and   embryonic   growth-differentiation 
processes) 

In  the  developmental  processes  inaugurated  at  conception  two  distinct 
phases  are  to  be  observed — growth  and  differentiation.  In  intra-uterine  life 
differentiation  into  specific  organs  and  tissues  is  the  essential  process.  In 
pre-adult  life,  growth  proces.ses  are  dominant.  At  puberty  differentiation 
again  asserts  its  influence.  In  adult  years  both  these  developmental  pro- 
cesses are  less  in  evidence,  a  condition  we  commonly  designated  as  maturity. 

These  two  phases  of  development  are  necessarily  intricately  interrelated, 
but  within  certain  limitations  may  be  separately  altered.  Traces  of  thyroid 
tissue  added  to  the  water  in  which  tadpoles  live  will  bring  about  the  com- 
plete transformation  of  the  tadpole  into  a  minature  frog  within  one  week, 
whereas  normally  this  metamrophosis  consumes  from  four  to  six  months. 
(Gudernatch.)  This  phenomenon  is  due  to  the  intense  differentiative  action 
of  the  thyroid.  Similarly  thymus  tissue  retards  differentiation  of  tadpoles. 
At  the  period  of  development  wherein  normally  tadpoles  begin  to  differen- 
tiate, thymus  fed  tadpoles  continue  to  grow  larger  without  differentiation. 
Manifestly  both  these  factors  in  development  are  ultimately  dependent  upon 
the  quantity  or  quality  of  cell  activity. 

In  our  earlier  records  of  the  influence  e.xerted  by  the  pineal  upon  devel- 
opment we  employed  young  animals  and  chicks.  \'ariations  were  intro- 
duced to  reduce  the  possibility  of  incidental  error  in  dosage,  in  method  of 
administration,  in  source  of  materials,  in  age  of  the  test  animals.  \\'ith  the 
exception  of  two  series  we  have  uniformly  found  that  young  animals  who 
had  been  fed  (or  injected)  pineal  materials  have  outgrown  their  controls 
of  the  same  age.  (Fig.  3.)  In  one  series  the  difference  was  40  per  cent,  at 
eleven  weeks  of  age.  No  tendency  to  gigantism  was  observed.  As  the  nor- 
mal adult  size  was  approached  the  stimulative  action  of  the  pineal  was  no 
longer  effective.     The  testes  of  certain  of  these  rapidly  developed  guinea 


CAREY  PRATT  McCORD 


pigs  were  examined  in  comparison  with  controls.  Grossly  the  testes  from 
pineal  fed  animals  were  SO  per  cent,  larger.  Microscopically  the  cellular 
elements  were  far  in  advance  of  controls  and  were  characterized  by  very 
active  spermatogenesis.  The  females  gave  birth  to  young  when  the  con- 
trols were  in  the  middle  third  of  their  gestation.  At  first  it  was  thought 
this  might  be  evidence  of  a  shortened  gestation  period,  but  more  carefully 
scrutinized  experiments  determined  that  this  was  the  outcome  of  earlier 
breeding,  due  to  an  earlier  maturity. 

At  all  times  this  type  of  feeding  experiment  is  open  to  the  error  that 
normally  such  animals  exhibit  very  appreciable  individual  variations.  We 
have  anticipated  that  less  complex  life  forms  that  show  scant  individual 
variations  even  in  large  numbers  would  afford  acceptable  data  as  to  any 
action  that  pineal  extracts  might  have  on  their  growth-differentiation  pro- 
cesses. For  the  purpose,  we  selected  (1)  paramoecia  (paramoecium  cau- 
datum),  a  unicellular  organism  that  through  transverse  fission  may  divide 
into  many  generations  in  a  single  day,  (2)  tadpoles)  of  frogs  and  toads. 
This  larval  form  of  the  frog  and  toad  corresponds  in  many  respects  to 
embr\onic  intrauterine  life  in  higher  animal  life. 

PAR.AMECIUM  EXPERIMENTS 

Cultures  were  maintained  in  the  laboratory,  growing  on  hay  infusions.  These 
organisms  are  aljout  '4  mm.  in  length  and  may  be  readily  counted  with  the  naked 
eye.  Through  transverse  splitting  reproduction  is  accomplished.  Under  standardized 
conditions  the  rate  of  divisions  is  relatively  constant.  It  will  be  argued  that  in  the 
event  of  constant  exceptional  variations  in  the  number  of  generations  formed  when 
pineal  materials  were  added  to  the  culture  medium  and  not  occurring  when  other 
similar  protein  materials  were  introduced,  that  the  phenomenon  is  attributable  to  pineal 
activity.  The  following  procedures  were  employed.  A  single  paramcecium  was  isolated 
until  the  reproduction  of  the  third  generation.  These  resulting  four  individuals  were 
separated  and  placed  in  difTerent  media  (a)  one  in  hay  infusion;  (h)  one  in  a  hay  in- 
fusion extract  of  desiccated  pineal  gland,  .05  per  cent,  strength;  (c)  one  in  a  hay  in- 
fusion extract  of  desiccated  muscle  of  equal  strength  as  a  control   material;    (rf)    the 

Tabu  I.     Records  of  Divisions  of   Paramoecia 


6 

7 

8 

9 
10 
II 
12 
1.^ 
14 
15 
16 
17 

Average 


'ineal 

Muscle 

No.   of 

Hay                  Pineal 

Muscle 

■,l.i„rt. 

Tissue. 

Kxpe'm't. 

Infusiuu. 

Gland. 

Tissue. 

^^ 

18 

13 

31 

19 

6 

12 

20 

1! 

19 

s 

21 

s 

2 

16 

22 

8 

8 

1.^ 

2} 

16 

4 

12 

24 

8 

5 

19 

12 

JS 

10 

17 

10 

12 

0 

26 

]  1 

19 

12 

4 

27 

7 

5 

9 

4 

28 

4 

3 

7 

6 

29 

7 

9 

19 

16 

30 

8 

2 

21 

1 ' 

31 

15 

s 

25 

23 

30 

10 

22 

11 

RANSOHOFF  MEMORIAL  VOLUME 


fourth  one  was  a  variable  control.  These  cultures  were  maintained  in  a  moist  cliamber 
for  a  fixed  period  (48  or  24  hours).  At  the  expiration  of  that  time  the  several  cultures 
were  examined  as  to  the  numbers  of  reproductions.  Almost  invariably  the  divisions 
were  more  numerous  in  the  pineal  culture.  For  example,  in  one  48-hour  experiment 
12  individuals  resulted  from  the  plain  hay  infusion,  30  individuals  from  the  hay  in- 
fusion pineal  extract  .05  per  cent,  and  10  individuals  from  the  hay  infusion  muscle 
extract  .05  per  cent.  The  results  from  31  consecutive  experiments  are  grouped  in 
table  1. 

The  inference  is.  that  pineal  materials,  when  added  to  the  culture 
medium  of  the  unicellular  orgaiusm,  ])arama"cium,  determines  a  more  rapid 
rate  of  reproduction.     (Fig.  4). 


TADPOLE  EXPERIMENTS. 
The  time  of  appearance  of  the  successtive  stages  in  the  differentiation 
of   tadpoles   into   frogs   is   an   excellent   criterion   of   the   influence   of    any 


Fig.  5.     A  comparison  of  luo  groups  of  t..a.l  tadpoles  taken   from  the  same  lot, 

photographed   simultaneously  after  two   weeks  of   lalioratory   feeding,     (iroup   to  the 

right  fed  small  amounts  of  desiccated  pineal  gland  triweekly.  Group  to  the  left  fed 
equivalent  amounts  of  desiccated  muscle  tissue. 

variation  in  the  living  conditions  of  these  animals.  For  the  individuals  of 
a  single  laying,  fairly  constant  is  the  occurrence  of  such  stages  as  the  bud- 
ding of  the  hind  legs  with  the  subsequent  formation  of  the  different  portions 
of  the  hind  legs,  the  closing  of  the  gills,  the  extrusion  of  the  fore  legs,  the 
assumption  of  terrestrial  life.  Such  are  the  phenomena  we  sought  to  influ- 
ence by  the  introduction  of  pineal  gland  materials  into  the  living  water  of 
the  tadpoles. 

About  50,000  frog  eggs  were  procured  and  hatched  in  the  laboratory. 
These  were  divided  into  colonies  of  about  200  each.  In  most  cases  these 
colonies  were  from  the  same  laying.  With  so  abundant  materials  it  was 
possible  to  introduce  wide  variations  in  (est  materials  and  controls.     The 


CAREY  PRATT  McCORD 


pineal  glands  were  fractionated  into  various  components  and  tested  against 
controls  such  as  other  endocrine  glands,  split  proteins,  histamine,  lipoids, 
etc.  Through  photography  and  actual  measurements  the  variations  were 
recorded. 

The  present  paper  can  make  but  most  casual  reference  to  the  accu- 
mulated results.  The  photograph  and  drawings  will  serve  to  indicate  the 
trend  of  results.  (Fig.  5.)  (Type  photograph — adjacent  trays  of  pineal 
fed  and  muscle  fed  tadpoles  of  the  same  laying.)  At  this  stage  the  pineal 
fed,  while  about  double  the  size  of  the  controls,  show  no  tendency  to  dififer- 


Fig.  6.  Drawings  madt-  at  weekly  intervals  indicating  the  rate  of  inetamorphosis 
of  Bufo  Americana  tadpoles  fed  pineal  tissue  in  comparison  with  normal  metamor- 
phosis, a  to  e  inclusive,  controls.  /  to  /,  pineal  fed.  The  small  figures  to  the  right, 
of  a,  b,  f  and  g,  represent  stages  in  the  development  of  the  hind  legs  for  these  respec- 
tive tadpoles. 

entiation.     Ultimately,   however,   differentiation   is   earlier,   as   may  be   ob- 
served in  the  drawings  of  Fig.  6. 

It  is  our  belief  that  the  pineal  gland  contains  some  substance  capable  of 
stimulating  growth  and  ultimately  diiTerentiation  in  these  larval  forms. 

GENERAL  SUMMARY. 
From  the  lack  of  unanimity  in  the  literature  any  conclusions  as  to  the 
details  of  pineal  gland  function  must  be  made  flexible  rather  than  dogmatic. 
A  survey  of  available  data  leads  to  the  following  summary  as  representing 
the  present  status  of  the  pineal  as  an  organ  of  internal  secretion : 


RAXSOHOFF  MEMORIAL  VOLUME 


1.  A  clinical  syndrome  is  to  be  associated  with  disturbances  of  the  func- 
tions of  the  pineal  gland.  Because  of  the  involution  of  the  pineal  at  puberty, 
the  constitutional  manifestations  of  pineal  pathology  appear  to  be  confined 
to  prepuberal  years.  The  essential  characteristics  (apart  from  pressure  and 
neighborhood  manifestations)  are  (a) early  sexual  development  evidenced 
in  the  enlarged  genitalia,  pubic  hair,  general  body  hair,  early  change  in 
voice;  (b)  precocious  mental  development,  manifested  in  maturity  of 
thought  and  speech;  (c)  general  overgrowth  of  body  to  the  extent  that  a 
child  of  six  or  seven  years  may  have  the  appearance  of  a  child  near  puberty. 

2.  The  experimental  extirpation  of  the  pineal  gland  is  surgically  pos- 
sible. The  gland  is  not  essential  for  the  maintenance  of  life.  The  early 
symptoms  following  pinealectomy  are  attributable  to  the  severe  brain  injury. 
No  changes  attend  the  removal  of  the  gland  in  adult  animals.  As  to  the 
effects  of  pinealectomy  in  young  animals,  Sarteschi,  Foa.  and  Horrax  respec- 
tively state  that  the  removal  of  the  gland  leads  to  precocity  of  development. 
Exner  and  Boese,  and  Dandy  report  no  changes  after  pinealectomy. 

3.  The  administration  of  pineal  substances  to  young  mammals  is  re- 
]iorted  to  hasten  growth  and  sexual  maturity.  In  unicellular  organisms 
(paramcEcia)  pineal  extracts  increase  the  rate  of  reproduction  to  more  than 
double  that  of  controls.  In  larval  forms  (ranidae)  both  growth  and  differ- 
entiation are  hastened  as  a  result  of  pineal  feeding. 

4.  The  inference  is  allowable  that  the  pineal  gland  is  an  organ  of  internal 
secretion  who.se  functions,  however,  are  of  minor  significance  in  the  general 
activities  of  the  endocrinous  system. 

BIBLIOGRAPHY. 

EXPn:RI.\IENT.AL 

.-\natomy   and   Embryology 

Beraneck,    E. :     Anat.   Anzeiger,    1892,  vii,   674.   Anat.    Anzeiger,    1893,  viii,   669. 
Biondi.    G. :     Histologische    Beobachtungen    an    der    Zirbeldriise,    Ztschr.    f.    d.    ges.    Neurol,    u 
Psychiat.,   1912,  ix,  43. 

Bizzozero,  G.:    Centralbl.  f.  d.  mcd.  Wissensch..   1871,  "R.  Istit.   Lomb.  di   Sc.  tt   Lett."     Milan. 


Cameron.  .lolin:     .Anat.    Anzeiger,   1903,   x.\iii.  Proc.   Roy.   Sec,   Edin.,   1904, 
"Jladrid, 


Ramon   y    C'ajal:     .\puntes   para   el   studio   del    bulbo   raquideo   cerebelo 
-  •■  OS,   Sue.   Es  ..•-■-.-       .   - 


Conslantini.   G. :    Pathologica 

Cionini,   A.:     "Riv.    Sperim.   d.   Fren.   e.   d.    .Med.   Legale,"    1885-86,  xi,    182;   xii,   364. 

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Verger.  M.:  Gliosarcoma  develope  an  niveau  de  la  glande  pineale.  Jour,  de  med.  de  Bordeaux, 
1907,  xxxvii,  216. 

Verger,  M.:  Teratom  und  Chorioephitheliom  der  Zirbeldruse,  Verhaiidl.  d.  deutsch.  path. 
Gesellsch.,  1906,  58. 

Vikhodtseff,  S.  N.:  Disease  of  Pineal  Body  with  Involvement  of  the  Eyes  and  Acromegaly, 
Vestnik   Ophthalmol.,    Moskow,    1913.    xx,    1014. 

Virchow,  R.:     Krankhafte  Geschwulste,   Berlin,   1863,   i.  ,   ^, 

Weed,   L.   H.,   and    Gushing,    H.:     Studies   on    Cerebrospinal    Fluid,    viii,    Amer.    Jour,    of   Pliysi- 

°  "''^Weigertr'c.V'  Zur  Lehre  von  den  Tumoren  der  Hirnanhiinge,  Virchow's  Arch.  f.  path.  Anat.. 
1875,   Ixv,   212. 

Wcrnick,  :     Lehrbuch   der   Gehirnkrankheiten,    1883,   iii,   299. 

WeisenburR,   T.   H.:    Brain,    1910,  xxxiii,   236. 

Wolf:  Zirhcldriisenextrakt  in  der  geburtsliilflchen  Landpraxis,  Deutsch.  med.  Wchnschr.,  1913, 
xxxix,   1557. 

Zenner,  A.:    A  Case  of  Tumor  of  the  Pineal   Gland,   Alienist   and   Neurol..    1892.   xiii,   470. 

Ziegler:     Lehrburch    der   patholovischen    Anatomie,    Ed.    4.    620. 


THE  NUCLEAUS  CARDIACUS  NER\1  \'AGI  AND  THE  THREE 
DISTINCT  TYPES  OF  NERVE  CELLS  WHICH  INNERVATE 
THE  THREE  DIFFERENT  TYPES  OF  MUSCLE..* 

Edward  F.  Malonu 

Cincinnati. 

THREE  FIGURES. 

When  one  lias  carefully  and  critically  studied  in  series  of  Nissl  prep- 
arations the  hrains  of  various  mammals,  there  is  revealed  the  presence  of 
con.stant  cell  groups  whose  cells  invariably  possess  certain  definite  charac- 
teristics as  to  size,  form  and  structure.  A  separation  of  two  groups  of  cells 
based  merely  upon  dififerences  in  their  histological  characters  is  justified  in 
the  present  state  of  our  knowledge,  only  when  such  dififerences  are  constant 
and  striking.  When  these  conditions  are  fulfilled  we  may  conclude  that 
such  constant  and  striking  dififerences  in  cell  character  correspond  to  a 
difiference  in  cell  activity,  just  as  in  other  portions  of  the  body.  I  have 
pointed  out  elsewhere  that  very  real  dififerences  in  cell  character  have  been 
neglected  by  experimental  workers,  and  that  their  results  have  been  rendered 
thereby  of  less  value.  Since  the  dorsal  motor  (sympathetic)  nucleus  of 
the  vagus  is  known  to  contain  centers  for  the  control  of  both  heart  muscle 
and  smooth  muscle,  one  would  suppose  that  any  real  difiference  in  the  cell 
character  of  various  portions  of  this  nucleus  would  at  once  claim  the  atten- 
tion of  the  experimental  worker  and  that  he  would  attempt  to  inform  us  as 
to  the  relation  of  these  dififerent  types  of  cells  to  the  various  functions  of 
the  vagus  nerve.  But  such  is  not  the  case ;  we  are  informed  casually  that 
some  cells  are  large  and  others  small,  and  thereafter  the  cells  are  consid- 
ered as  if  they  were  all  of  the  same  type. 

The  discovery  of  two  dififerent  types  of  cells  in  the  sympathetic  vagus 
nucleus  was  not  accidental ;  I  was  led  to  look  for  this  difiference  on  the 
following  grounds.  In  the  first  place.  I  had  recently  shown  that  all  cells 
concerned  in  transmitting  efferent  impulses  to  striated  muscle  possess  a 
fundamental  similarity  of  structure,  whether  the  a.xone  of  the  cell  be  in 
direct  relation  to  the  muscle  or  whether  the  cell  act  on  the  muscle  through 
the  mediation  of  one  or  more  efiferent  neurones.  This  observation  naturally 
strengthened  my  belief  in  the  significance  of  the  relation  of  cell  character 
to  cell  function.  In  the  second  place,  I  had  observed  the  striking  difiference 
between  the  cells  supplying  striated  and  those  supplying  smooth  muscle. 
Since  in  a  recent  paper  Molhant  had  shown  that  all  fibers  of  the  vagus 
supplying  heart  and  smooth  muscle  arise  from  the  sympathetic  vagus  nu- 
cleus, I  concluded  that  in  cells  having  such  diverse  functions  there  must 
exist  a  fundamental  difiference  in  histological  character.  As  was  anticipated, 
two  different  types  of  cells  were  found ;  the  evidence  in  favor  of  ascribing 
to  the  cells  of  one  type  the  innervation  of  heart  muscle,  and  on  the  other 


EDWARD  P.  MALONE 


hand,  to  cells  of  the  other  type  the  innervation  of  smooth  muscle,  will  be 
considered  later. 

The  material  available  consisted  of  two  complete  series.  The  first  was 
a  series  of  the  brain  of  a  lemur,  while  the  second  was  of  the  brain  of 
macacus  rhesus.  Both  brains  were  fixed  in  95  per  cent,  alcohol,  and  after 
the  usual  treatment  with  absolute  and  chloroform,  were  imbedded  in  par- 
affin. Serial  sections  were  stained  in  a  1  per  cent,  aqueous  solution  of 
toluidin  blue  (Griibler),  differentiated  in  95  per  cent,  alcohol,  dehydrated 
in  absolute,  cleared  in  xylol,  and  mounted  in  Canada  balsam.  Series  of 
brains  of  other  forms  will  have  to  be  prepared  and  studied  before  I  feel 
justified  in  committing  myself  upon  many  points,  and  the  present  article 
has  therefore  been  limited,  especially  as  to  the  exact  location  and  distribu- 
tion of  the  dilferent  types  of  cells. 

'J'he  efiferent  fibers  of  the  vagus  nerve  arise  from  two  distinct  columns 
of  cells.  From  the  nucleus  ambiguous  arise  the  fibers  which  supply  striated 
muscle,  while  from  the  so-called  dorsal  motor  nucleus  arise  fibers  which 
innervate  heart  muscle  and  smooth  muscle.  This  fundamental  difference  as 
to  function,  which  has  been  proved  beyond  doubt  by  the  recent  investiga- 
tion of  Molhant,  had  not  been  clearly  recognized ;  this  obscurity  was  prob- 
ably favored  by  the  fact  that  the  nucleus  ambiguous,  together  with  the 
motor  nuclei  of  the  eleventh,  seventh  and  fifth  cranial  nerves  have  often 
been  regraded  as  visceral,  regardless  of  the  fact  that  their  cells  cannot  be 
distinguished  either  histologically  or  functionally  from  the  cells  of  the 
other  motor  nerves  supplying  striated  muscle.  Thus  this  classification  giv- 
ing undue  emphasis  to  a  condition  which  in  mammals  no  longer  exists,  has 
contributed  to  the  general  lack  of  appreciation  that  the  dorsal  motor  nucleus 
of  the  vagus  is  composed  of  cells  which  ditifer  radically  both  histologically 
and  functionally  from  those  of  the  nuclei  supi)lying  striated  muscle,  regard- 
less of  whether  the  striated  muscle  be  of  somatic  or  of  visceral  origin.  The 
name  "dorsal  motor  nucleus"  does  not  indicate  the  true  function  of  this 
cell  group,  and  I  shall  use  the  name  "sympathetic  or  visceral  luicleus  of  iht 
vagus." 

The  location  and  extent  of  the  .sympathetic  nucleus  of  the  vagus  is  well 
known  and  will  not  be  considered  in  this  paper,  except  to  call  attention  to 
the  fact  that  it  extends  as  a  long  column  of  cells  dorso-lateral  to  the  hy]io- , 
glossus  nucleus  from  the  lowest  portion  of  the  medulla  to  almost  the  level 
of  the  oral  i)ole  of  the  inferior  olive.  An  excellent  description  of  the  loca- 
tion of  this  nucleus  is  given  in  Jacobsohn's  monograph.  The  oral  portion 
of  the  nucleus  is  composed  of  small  cells  of  the  type  shown  in  figure  2; 
this  is  true  both  in  the  ca.se  of  the  lemur  and  the  monkey.  As  one  follows 
the  nucleus  caudally  a  second  type  of  cell  begins  to  appear  (Fig.  1).  The 
portion  of  the  nucleus  in  which  both  types  of  cells  occur  is  at  the  level  of  the 
oral  portion  of  the  hypoglossus  nucleus,  and  here  the  sympathetic  nucleus 
attains  its  greatest  diameter.  The  cells  of  each  type  are  partly  .separated 
from  each  other,  although  no  sharp  line  of  separation  is  evident.     In  the 

Page   „";.'■ 


KANSOHOff  MEMORIAL  VOLUME 


lemur  the  large  cells  (Fig.  1)  form  a  fairly  compact  group  dorsal  from 
the  small  cells,  whereas  in  the  monkey  their  relative  position  is  reversed. 
Proceeding  further  in  a  caudal  direction,  the  small  cells  become  rapidly  less 
numerous  and  finally  disappear.  After  the  disappearance  of  the  small  cells 
the  sympathetic  nucleus,  consisting  now  entirely  of  the  large  cells  (Fig.  1) 
proceeds  caudally  as  a  well  developed  and  definite  group.  In  the  most  caudal 
portion  of  the  medulla  the  sympathetic  nucleus  is  much  reduced ;  only  a 
few  cells  are  seen  in  each  section,  and  these  cells  become  smaller  and  have 
the  appearance  of  the  smallest  cell  in  figure  1  ;  in  this  portion  of  the 
nucleus  (the  caudal  end)  are  probably  also  cells  of  the  type  shown  in  figure 
2,  that  is,  similar  to  those  in  the  oral  portion  of  the  nucleus,  but  at  present 
I  cannot  be  absolutely  sure  of  this,  as  the  surrounding  cell  groups  have  not 
been  sufficiently  studied.  The  smallest  cell  shown  in  figure  1  is  probably 
a  transition  type  between  the  other  cells  of  figure  1,  and  those  of  figure  Z. 
To  sum  up,  the  sympathetic  vagus  nucleus  consists  of  three  portions  :  (a)  an 
oral  portion  whose  cells  are  of  the  type  in  figure  2;  (b)  a  middle  portion 
whose  cells  are  shown  in  figure  I ;  and  (c)  a  caudal  portion  composed  of 
cells  shown  in  figure  2  (same  as  oral  portion)  and  also  of  cells  such  as  the 
smallest  cell  in  figure  1  (probably  a  transition  type). 

It  is  not  my  intention  to  present  in  this  paper  a  detailed  description  ol 
the  types  of  cells  in  the  vagus  symjiathetic  nucleus,  but  rather  to  point  out 
the  fact  that  there  are  very  definite  differences  in  histological  character 
between  the  cells  of  the  various  groups ;  a  study  of  the  illustrations  will 
make  this  evident.  Since  these  differences  in  cell  character  exist,  and  since 
such  differences  must  necessarily  be  an  indication  of  corresponding  differ- 
ences of  cell  activity,  we  may  now  consider  whether  these  different  cell 
groups  of  diflferent  character  may  be  brought  into  relation  with  definite 
functions.  In  the  first  place,  it,  has  been  shown  by  Molhant,  in  his  excel- 
lent and  extensive  work  on  the  vagus  nerve,  that  the  sympathetic  nucleus 
of  the  vagus  gives  origin  to  all  the  fibers  of  the  vagus  which  supply  smooth 
and  heart  muscle,  and  that  all  its  cells  give  origin  to  such  fibers.  Further, 
he  has  shown  that  the  oral  portion  supplies  smooth  muscle  (stomach,  lungs), 
the  function  of  the  extreme  caudal  portion  is  doubtful  (possibly  connected 
with  the  trachea  and  bronchi),  while  the  intermediate  portion  supplies  heart 
muscle,  but  he  has  failed  to  connect  these  different  functions  with  different 
types  of  cells.  Concerning  the  function  of  the  caudal  portion  of  the  nucleus, 
which  is  composed  of  cells  of  the  type  shown  in  figure  2,  together  with  cells 
resembling  the  smallest  cell  of  figure  1,  we  can  draw  no  definite  conclusion. 
The  oral  portion  consists  exclusively  of  the  type  of  cells  .shown  in  figure  2, 
and  we  may  conclude  that  this  type  of  cell  supplies  smooth  muscle ;  of 
course  this  does  not  justify  us  in  concluding  that  this  type  of  cell  (Fig.  2) 
is  the  only  type  of  cell  which  may  supply  smooth  muscle,  or  that  this  type 
may  not  in  other  regions  have  a  different  function.  Overlapping  the  cells 
supplying  smooth  muscle  (Fig.  2)  and  extending  caudally  unaccompanied 
by  other  types  of  cells  is  the  type  of  cell  shown  in  figure  1.  and  this  portion 


EDWARD  F.  MALONE 


of  the  S)'nipathetic  nucleus  lias  been  shown  (Molhant)  to  supply  heart 
muscle. 

It  is  evident  therefore  that  the  cells  of  figure  1  supply  heart  muscle, 
while  those  of  figure  2  supply  smooth  muscle  (stomach  and  lungs).  In 
addition  there  is  purely  histological  evidence  to  support  the  functional  rela- 
tions of  these  two  types  of  cells  (Figs.  1  and  2),  since  the  cells  supplying 
heart  muscle  (Fig.  1)  are  a  type  intermediate  in  histological  structure  bc- 
tiveen  those  supplying  smooth  muscle  (Fig.  2)  and  those  supplying  striated 
muscle  (cells  of  hypoglossus  nucleus,  Fig.  3).  The  relative  size  of  the 
Nissl  bodies  in  the  three  types  of  motor  cells  illustrated  in  figures  1  to  3 
is  especially  worthy  of  notice.  The  fact  that  nerve  cells  supplying  heart 
muscle  are  of  a  type  intermediate  between  those  supplying  striated  and 
smooth  muscle  constitutes  one  of  the  strongest  arguments  in  support  of 
the  importance  of  the  relation  of  cell  character  to  cell  function,  since  heart 
muscle  is  histologically  intermediate  between  the  two  other  types  of  muscle. 

The  cell  group  which  supplies  heart  muscle,  composed  of  the  character- 
istic cells  shown  in  figure  1,  I  shall  name  provisionally  "nucleus  cardiacus 
nervi  vagi."  I  do  not  feel  justified  in  assigning  any  name  to  the  other  por- 
tions of  the  vagus  sympathetic  nucleus,  but  shall  be  content  with  pointing 
out  that  the  cells  of  the  oral  portion  which  supply  smooth  muscle  are  of  a 
definite  type  (Fig.  2).  A  further  division  is  at  present  not  advisable  be- 
cause the  functional  relations  of  the  caudal  group  are  not  understood,  and 
because  the  pigmented  cells  described  by  Jacobsohn  in  man,  have  not  been 
identified  and  studied  (of  course,  in  lower  animals  pigment  is  wanting, 
although  homologous  non-pigmented  cells  may  e.xist).  Further  subdivision 
of  the  sympathetic  nucleus,  together  with  a  detailed  description  of  the  loca- 
tion and  extent  of  the  various  cell  types,  the  consideration  of  transition 
types,  and  of  the  relations  of  the  nucleus  to  the  cells  of  surrounding  nuclei, 
must  await  a  thorough  study  of  numerous  series  of  various  aninnls  (includ- 
ing man). 

CONCLUSIONS. 

1.  The  histological  character  of  a  nerve  cell  is  an  indication  of  its  func- 
tion. Dififerences  in  connections  with  portions  of  the  organism  which 
differ  merely  in  spatial  relations  do  not  involve  a  difTerence  in  the  character 
of  the  nerve  cells,  but  are  associated  merely  with  the  location  of  the  nerve 
cell;  for  instance,  arm  and  leg  muscles,  flexors  and  extensors  are  all  inner- 
vated by  the  same  type  of  cell,  although  such  dififerences  in  peripheral  con- 
nections correspond  to  differences  in  the  position  of  the  corresponding 
nerve  cells.  * 

2.  The  three  types  of  muscle  are  innervated  by  three  distinct  type  of 
nerve  cell,  which,  however,  are  related  to  one  another  in  such  a  manner 
that  the  cell  innervating  heart  muscle  is  of  a  type  intermediate  between  the 
other  two  types  of  cells.  Heart  muscle,  smooth  muscle,  and  striated  muscle 
are  innervated  by  cells  such  as  are  illustrated  in  figures  1,  2  and  3  respec- 


RA.YSOHOFF  MEMORIAL  VOLUME 


NUCLEUS  CARDIACUS  NERVI  VAGI 
KinvARii  F.  Malonr 


Explanation  of  Figures. 

1  to  .1  Tile  ceHs  illustrated  in  the  three  figures  were  all  drawn  from  the  same 
section  witli  the  aid  of  the  camera  lucida.  and  for  all  cells  the  magnilication  is  580 
diameters.  1  have  attempted  to  reproduce  as  nearly  as  possible  the  actual  appearance 
of  the  cells,  combining  to  a  certain  extent  ditTerent  levels  of  focus.  These  three 
figures  clearly  show  that  the  cells  supplying  heart  muscle  (Fig.  1)  are  histologically 
intermediate  between  the  cells  supplying  smooth  muscle  (Fig.  2)  and  those  supplying 
striated  muscle  (Fig.  3). 

1.  Cells  from  nucleus  cardiacus  nervi  vagi  of  lemur.  The  smallest  cell  represents 
probably  a  transition  type  to  the  cell  type  of  figure  2,  and  this  type  occurs  more  fre- 
quently in  the  caudal  portion  of  the  vagus  sympathetic  nucleus  where  it  is  found 
together  with  the  cells  of  the  type  shown  is  figure  2.    580  diameters. 

2.  Cells  of  vagus  sympathetic  nucleus  of  lemur  which  innervate  smooth  muscle. 
In  the  oral  portion  of  the  sympathetic  vagus  nucleus  these  cells  occur  alone;  more 
caudally  they  oceur  i.if^ttlur  with  the  cells  of  the  nucleus  cardiacus  (Fig.  1)  in  the 
most  oral  portion  <<i  this  nm  leus.  In  the  caudal  portion  of  the  sympathetic  nucleus 
such  cells  probabl)  reappear  and  are  accompanied  liy  the  small  cell  type  shown  in 
figure  I   (smallest  cell).     580  diameters. 

3.  Cells  from  hypoglossus  nucleus  of  lemur,  innervating  striated  muscle.  580 
diameters. 

Pagc'37S 


EDWARD  F.  MALONE 


lively,  the  cells   of   figtire    1   constituting  a  type  intermediate  between   the 
other  two. 

3.  The  nucleus  cardiacus  nervi  vagi  is  situated  in  the  middle  portion  of 
the  sympathetic  nucleus  of  the  vagus  and  is  composed  of  cells  shown  in 
figure  1. 

4.  The  time  has  passed  when  experimental  workers  can  afford  to  neg- 
lect to  inform  themselves  of  the  existence  of  deiinite  types  of  cells  situated 
in  the  region  under  investigation,  and  to  attempt  to  bring  cell  character  into 
relation  with  cell  function. 


I)IBUOGR.\PHY. 

Jacnbsnr 

1.  r,.. 

1909: 

t'hei-    dif 

■   Kern 

e   de5   menschUchen   H 

Ahlmidlnnce 

r    krtniel 

.\ka 

d.    d.    Wis<. 

Malone. 

K., 

1910:      1 

'her   die 

Kerne 

des  menschlichen   l)l( 

.\blmndluni!e 

n   del 

koniel. 

.\kad. 

d.  Wis,. 

Malone. 

K.. 

191.1: 

Rerognlt 

ion    of 

members   of   the   son 

.■\nat.   Rec,  . 

vn\.    7 

.  Xo.  3. 

Mnlhant 

.    M-, 

1910: 

Le  nerf 

vague 

:    (priniiere   partie(. 

MnHianl 

,   M., 

et  Van 

Gphuclit 

en,  A. 

,   1912:     Contribution 

,\  PHARMACOLOGICAL  STUDY  OF  BENZYL  BENZOATE.* 

By  Edwakd  C.  Mason.  A.  11..  M.  1).,  and  Cari,  E.  Pikck.  B.  S., 

Cincinnati. 

The  recent  introduction  of  benzyl  benzoate  to  the  medical  profession, 
and  the  apparently  increasing  demand  for  the  .substance  have  led  us  to  under- 
take the  present  .studv  in  the  hope  of  adding  some  further  contribution  to 
our  knowledge  of  the  pharmacologic  action  of  the  body.  With  reference  to 
this  type  of  benzyl  derivatives  it  lias  already  been  stated  by  Macht  that 
"inasmuch  as  they  arc  practically  insoluble  in  water,  pharmacologic  experi- 
ments with  them  could  not  be  performed  on  isolated  tissue  in  z'itro  except 
imder  special  conditions."  We  have,  of  course,  been  confronted  with  this 
difficulty  in  carrying  out  the  present  experiments  which  have  been  performed 
entirely  on  the  intact  animal,  since  Macht,'  in  his  splendid  work  on  this  sub- 
ject, has  probably  done  all  that  would  yield  valuable  information  through 
working  with  isolated  tissues. 

Three  different  preparations  were  used  in  the  course  of  this  work.  They 
were  sold  by  the  following  firms :  Hynson,  \^'estcott  and  Dunning.  Balti- 
more;  The  Norwich  Pharmacal  Co.,  Norwich,  N.  Y.,  and  \^an  Dyke  and  Co.. 
New  York.  These  three  preparations  varied  somewhat  in  toxicity,  and  con- 
siderably in  their  property  of  remaining  in  solution.  However,  the  pharma- 
cologic effects  produced  were  quite  the  same.  By  testing  the  action  on  drawn 
blood  we  found  that  these  commercial  20  per  cent,  preparations  exercised  a 
pronounced  action  on  the  drawn  blood,  and  for  that  reason  we  have  used 
the  20  per  cent,  preparations  diluted  with  an  equal  volume  of  water.  We 
found  this  10  per  cent,  dilution  very  satisfactory  for  intravenous  injection. 
In  many  of  our  records  the  term  "saturated  water  emulsion"  is  used  and  is 
not  technically  correct,  but  refers  to  the  10  per  cent,  solution  just  described. 

In  the  recent  medical  literature-  a  considerable  number  and  variety  of 
clinical  conditions  are  described  as  having  been  benefited,  often  in  a  very 
striking  manner,  by  the  use  of  the  benzyl  esters.  Among  these  conditions 
may  be  mentioned  (1)  excessive  peristalsis  of  the  intestine,  as  in  diarrhea 
and  dysentery,  (2)  intestinal  colic  and  entero.spasm,  (3)  pylorospasm,  (4) 
spastic  constipation  in  which  there  was  a  tonic  spastic  condition  of  the  intes- 
tine, (5)  biliary  colic,  (6)  ureteral  or  renal  colic,  (7)  vesical  spasm  of  the 
urinary  bladder,  (8)  spasmodic  pains  originating  froiu  the  contraction  of 
the  seminal  vesicles,  (9)  uterine  colic,  (10)  arterial  spasm,  including  hyper- 
tension or  high  blood  pressure,  (11)  bronchial  spasm.  It  has  been  our  aim 
in  this  study  to  shed  some  light,  if  possible,  on  the  mechanism  by  which 
these  conditions  are  relieved,  and  to  ascertain  the  concentration  of  the  drug 
in  the  blood  necessary  to  produce  the  desired  results. 

It  will  be  noted  that  the  first  four  clinical  conditions  listed  above  refer 
to  increased  activity  or  increased  tonus  of  the  intestinal  tract.     We  have 


"From   thp  PhartnacoloRica!   I^alioratory   of   the    t.'niversitv   of   Cincinnati   Medical    School.    Cii 
cinnati.  Ohio.  From  the  Journal   of  Laboratory  and   Clinical   Medicine,   November,    1920. 
Page  m 


EDWARD  C.  MASON  AND  CARL  E.  PIECK 


RANSOHUFF  MEMORIAL  VOLUME 


therefore  felt  it  desirable  to  study  the  nature  of  the  relaxation  produced  by 
the  benzyl  benzoate  in  these  conditions.  Figure  1  shows  the  respiration, 
right  carotid  pressure  and  pylorus  contractions  in  a  dog  weighing  13  kilos. 
Near  the  beginning  (left)  of  the  tracing  2  cc.  benzyl  benzoate  solution  was 
injected  into  the  femoral  vein.  This  produced  no  appreciable  change  in  the 
rate  or  amplitude  of  either  the  pyloric  contractions  or  the  respiration.  There 
is  perhaps  a   slight  chansje  in  the  blood  pressure  tracing.     Following  this 


irc-^c.CXv'^ 


I'igure  2. 

4  cc.  of  the  benzvl  benzoate  solution  was  injected  and  this  produced  a  depres- 
sion of  the  respiration,  an  obvious  fall  in  blood  pressure  and  perhaps  a  very 
slight  inhibitory  effect  on  the  pyloric  contractions.  An  injection  of  1  cc.  of 
adrenaline  (1-10.000)  was  now  given  as  a  check  on  the  technic  of  the  experi- 
ment. This  produced  a  very  obvious,  but  rather  brief,  inhibition  of  the 
pyloric  contractions.  When  the  animal  again  returned  to  normal  a  further 
injection  of  6  cc.  of  benzyl  benzoate  was  given.     After  a  brief  interval  this 


EDWA RD  C.  MASON  AND  CARL  E.  PIECK 

dosage  produced  complete  relaxation  of  the  pylorus,  but  simultaneously  it 
caused  the  death  of  the  animal,  apparently  by  central  respiratory  paralysis. 
This  tracing  shows  very  well  the  progressive  effects  of  small,  medium  and 
large  doses  of  the  drug.  The  marked  slowing  of  the  heart  following  the 
4  cc.  injection  should  be  noted. 

In  order  to  get  further  information  regarding  the  action  of  the  drug  on 
the  intestinal  walls  we  carried  out  a  series  of  experiments  as  illustrated  in 


Fig.  2.  In  this  case  a  .small  rubber  balloon  (finger  cot)  filled  with  wafer 
was  placed  within  the  intestinal  lumen  and  connected  by  rubber  tubing  with 
a  burette  which  carried  a  stopper  in  the  upper  end.  From  the  stopper  a  rub- 
ber tube  led  to  the  recording  tambour.  The  water  filled  the  balloon  and 
reached  about  two  inches  up  in  the  burette,  the  upper  part  of  which  was 
filled  with  air.  Thus  contractions  which  lessened  the  lumen  of  the  intestine 
caused  the  writing  point  of  the  tambour  to  rise,  and  relaxation  of  the  gut 
showed  a   fall  in  the  kymograph  tracing.     In  the  beginning  a  small  dose 

Paoc  i-,1 


RANSOHOFF  MEMORIAL  VOLUME 


(one  half  cc.  of  .5  per  cent  solution)  of  barium  chloride  was  injected  to 
stir  up  marked  contractions  of  the  intestine.  The  marked  rise  in  tone  of 
the  intestine  is  well  shown  in  the  tracing.  When  the  circular  musculature 
of  the  gut  was  well  contracted  an  injection  of  2  cc.  of  benzyl  benzoate  was 


given.  This  depressed  the  respiration  and  slightly  lowered  the  blood  pres- 
sure, but  produced  no  immediate  change  in  the  tone  of  the  intestine. 
After  an  interval  of  about  one  minute,  however,  there  occurred  a  relaxation 
of  the  intestine  and  at  this  point  a  further  injection  of  2  cc.  of  the  drug 


EDWARD  C.  MASON  AND  CARL  E.  PIECK 


was  given.  This  apparently  slightly  increased  the  tonus  of  the  intestine  and 
was  followed  liv  a  series  of  small,  irregular  contractions.  As  a  check  on 
the  technic  of  the  experiment  an  injection  of  one-half  cc.  of  adrenalin  was 


finalh  t^ui-u  1  hl^  pioikKcd  an  immediate  and  complete  relaxation  of  the 
gut  It  will  be  noted  that  the  second  injection  of  benzyl  benzoate  greatly 
depressed  the  respiiation,  but  both  injections  of  benzyl  benzoate  taken  to- 

Page  STB 


RANSOHOFF  MEMORIAL  VOLUME 


o-ether  were  very  much  less  effective  in  lowering  the  tone  of  the  intestinal 
musculature  than  was  the  one-half  cc.  of  1-10,000  adrenaline  solution. 

The  injection  of  a  sufficiently  large  dose  of  benzyl  benzoate  is  followed 
by  a  prompt,  ]ironounced  and  prolonged  fall  of  blood  pressure.     From  the 


nature  of  the  blood  pressure  curve  produced,  we  early  conceived  the  idea 
that  the  heart  played  an  important  part  in  this  lowering  of  the  arterial  ten- 
sion. Figure  3  shows  a  tracing  taken  directly  from  the  heart  (upper  curve; 
myocardiograph)  and  the  right  carotid  pressure  tracing.  It  will  be  noted 
that  2  Gc.  of  benzyl  benzoate  gave  little  or  no  change,  but  that  4  cc.  pro- 


EDWARD  C.  MASON  AND  CARL  E.  PIECK 


duced  the  characteristic  fall  in  blood  pressure.  It  is  obvious  that  this  fall  in 
pressure  is  closely  associated  with  the  changes  in  the  amplitude  and  f«rce 
of  the  heart  beat.  But  in  order  to  analyze  this  point  still  further  we  present 
Fig.  4,  in  which  the  drum  was  made  to  revolve  much  more  rapidly  than  in 
Fig.  3.  Fig.  4  shows  that  3  cc.  of  the  drug  was  followed  by  a  fall  in 
blood  pressure,  but  ihat  the  heart  at  the  same  time  became  weak  and  after 


an  interval  came  near  stopping  in  diastole.  After  a  prolonged  series  of 
feeble,  irregular  beats,  however,  the  heart  again  recovered  slightly,  and  the 
blood  pressure  finally  became  somewhat  more  regular.  These  changes  in 
the  blood  pressure  are  obviously  due  to  a  weakening  action  of  the  drug  on 
the  heart.  It  .should  be  noted  that  this  animal  was  receiving  artificial  res- 
piration. 

Fig.  5  shows  the  action  of  benzyl  benzoate  on  the  respiration,  spleen  vol- 
ume and  blood  pressure  of  a  dog  weighing  6.5  kilos.     In  order  to  produce  a 

Page  m 


RANSOHOFF  MEMORIAL  VOLUME 


tonus  in  the  spleen  an  injection  of  1  cc.  of  .5  per  cent.  Ijarinm  chloride  was 
giveh  at  the  beginning  of  the  tracing.  The  contraction  of  the  spleen  became 
very  marked  and  this  was  followed  after  a  time  by  some  relaxation.  Four 
cc.  of  benzyl  benzoate  was  now  injected  in  order  to  see  whether  or  not  the 
drug  would  relax  the  spleen.  It  will  be  noted  that  the  spleen  (oncometer) 
tracing  again  dips  even  lower  than  it  did  following  the  marked  contraction 
produced  by  the  barium  chloride.  But  the  causes  of  these  two  spleen  con- 
tractions are,  however,  exactly  the  opposite  of  each  other.  In  the  first,  the 
shrinkage  of  the  spleen  volume  represents  an  active  contraction  of  smooth 


^-A^^wCU^ 


\l3:.c-i^iC_\ 


m..^ 


"^^^^^^"^ 


:iL.^,-^j»>H*.,^ju. 


muscle  within  the  spleen.  The  second  contraction  is  passive,  and  is  due  to 
the  profound  fall  in  blood  jiressure.  and  perhaps,  somewhat  to  the  asphyxia 
which  followed  the  injection  of  the  benzyl  benzoate.  Artificial  respiration 
was  started  at  "1"  and  stopped  at  "2."  Although  the  blood  pressure  again 
returned  to  a  high  tension  (continued  action  of  the  barium)  and  the  spleen 
tracing  also  marked  a  low  level  (also  barium  contraction),  still  there  is  no 
evidence  that  the  benzyl  benzoate  exercised  any  relaxing  action  on  the  spleen. 
although  the  dosage  was  perhaps  sufificient  to  have  killed  the  animal  if  arti- 
ficial respiration  had  not  been  given.  Under  artificial  respiration  animals 
can  withstand  very  nuich  larger  doses  of  the  drug  without  dying,  than  is 
possible  under  natural  respiration.     This  indicates  that  the  animals  do  not 

Page  3Si 


EDWARD  C.  MASON  AND  CARL  E.  PIECK 


die  of  thrombosis  as  might  be  suspected  from  the  rather  unsatisfactory 
character  of  the  drug  for  intravenous  injection.  The  final  recovery  of  the 
heart  and  circulation,  if  artificial  respiration  be  maintained,  shows  that  no 
permanent  thrombi  are  lodged  in  any  vitally  important  vascular  areas. 

Fig.  6  shows  the  respiration,  kidney  volume  (oncometer)  and  blood  pres- 
sure. In  the  beginning  4  cc.  of  benzyl  benzoate  solution  was  injected.  Slight 
eiTects  were  produced  in  all  three  tracings.  The  small  shrinkage  in  kidney 
volume  is  obviously  secondary,  and  due  to  the  fall  in  blood  pressure.     If  the 


arterioles  themselves  in  the  kidney  had  dilated  the  volume  record  would  have 
risen,  as  occurs  after  the  constriction  produced  by  the  1  cc.  injection  of 
adrenalin  (at  the  center  of  the  tracing)  begins  to  wear  off.  The  shrinkage 
of  the  kidney  volume  after  the  adrenaline  is  active  and  is  due  tO'  the  adrena- 
line stimulating  the  myoneural  junctions  of  the  vasoconstrictor  nerves  in 
the  renal  arterioles.  Following  the  adrenaline  a  further  dose  of  7  cc.  of 
benzyl  benzoate  was  given.  The  results  of  this  were  exactly  analogous  to 
those  produced  by  the  4  cc,  but  were  correspondingly  more  pronoimced. 


RANSOHOFF  MEMORIAL  VOLUME 


11ie  recently  suggested  use  of  benzyl  benzoate  in  clinical  conditions  pre- 
sumably dependent"  on  excessive  or  abnormal  contraction  of  the  uterus^ 
indicated  that  the  drug  would  probably  produce  relaxation  of  this  organ. 
Figs  7  and  8  show  the  results  we  have  obtained  in  the  study  of  the  action 
of  the  .Irucr  on  this  organ.     In  Fig.  7  an  injection  of  3  cc.  was  made  and 


produced  verv  obvious  results  on  the  respiration  and  blood  pressure.  On  the 
uterus,  howe;er,  the  results  are  very  slight.  Fig.  8  also  shows  the  effects  of 
an  injection  of  5  cc.  of  the  drug.  This  dosage  finally  stopped  the  uterine 
contractions,  but  not  until  the  animal  had  died.     Obviously  one  could  not 


such  large  aiiK 


of  the  drug.  This  dosage  hnally  stopped  tne  urerine 
until  the  animal  had  died.  Obviously  one  could  not 
nts  clinicallv.      In  these  tracings  the  uterus   remained 


EDWARD  C.  MASON  AND  CARL  E.  PIECK 


RANSOM  OFF  MEMORIAL  VOLUME 


in  situ  and  great  care  was  used  not  to  disturb  its  innervation  or  blood  supply, 
and  to  keep  the  organ  warm  and  moist  by  closing  the  abdominal  wall  and 
covering  the  recording  apparatus  with  the  intestines  (see  Jour.  Lab.  and 
Clin.  Med..  1917,  iii,  63).    In  regard  to  these  two  records,  however,  it  should 


Figure 


be  stated  that  it  is  often  difficult  to  secure  entirely  satisfactory  tracings  of 
the  uterus  in  situ  in  dogs,  and  we  should  not  be  inclined  to  lay  too  great  em- 
phasis on  these  observations  without  checking  the  results  by  a  considerable 
number  of  experiments  on  animals  of  ditTerent  species,  which  we  have  not 


EDWARD  C.  MASON  AND  CARL  E.  FIECK 


as  yet  had  an  opportunity  to  do.    In  our  present  experiments  the  uterus  had 
previously  been  roused  to  increased  activity  by  the  injection  of  pituitrin. 

One  of  the  most  important  cHnical  uses  suggested  for  benzyl  benzoate  is 
in  the  treatment  of  bronchial  asthma.*  Fig.  9  represents  two  tracing  taken 
from  separate  dogs  and  mounted  together.  They  show  the  action  in  spinal 
dogs  of  histamine  (B-iminazolylethylamine,  "ergamine").  benzyl  benzoate, 
codeine  and  adrenaline  on  the  bronchioles  as  recorded  by  a  special  aspira- 
tion method  (see  Jour.  Pharmacol,  and  Exper.  Therap.,  1914,  vi,  57;  also, 


Jackson's  Experimental  Pharmacology,  C.  V.  Mosby  Co.,  1917.  St.  Louis, 
p.  287).  In  these  tracings  (also  Figs.  10  and  11)  a  shortening  of  the  ampli- 
tude of  the  lung  record  means  contraction  of  the  bronchioles,  and  increase  in 
the  amplitude  of  the  lung  tracing  shows  dilatation  of  the  bronchioles.  In 
Fig.  9  the  left  hand  record  shows  a  contraction  of  the  bronchioles  produced 
by  the  intravenous  injection  of  two-thirds  milligram  of  ergamine.  This  led 
to  a  bronchial  contraction  which  10  cc.  and,  later  30  cc.  of  an  aqueous  solu- 
tion of  benzyl  benzoate  did  not  relax.     An  injection  of  adrenaline  (2  cc.) 

Page  3S7 


RASSOHOFF  MEMORIAL  VOLUME 


produced  prompt  bronchial  dilatation.  In  the  right  hand  tracing  codeine  was 
used  to  produce  the  initial  bronchial  contraction  and  then  3  cc.  of  the  20 
per  cent  benzoate  made  up  in  75  per  cent,  alcohol  was  injected  mtravenously. 


The  dog  weighed  8  kilos  and  it  would  appear  that  this  dosage  should  cer- 
tainly have  caused  dilatation  of  the  bronchioles.  This  did  not  occur,  how- 
ever and  as  a  further  check  on  the  technic  of  the  experiment  2  cc.  of  adrena- 


EDWARD  C.  MASON  AND  CARL  E.  PIECK 


lin  was  injected.  A  bronchial  dilatation  followed  although  the  heart  stopped 
beating  (from  the  eflfects  of  the  codeine  and  benzyl  benzoate).  Fig.  10 
shows  that  2  cc.  of  pure  benzyl  benzoate  (made  by  the  Harmer  Laborator- 
ies) did  not  produce  the  slightest  indication  of  a  bronchial  dilatation  follow- 
ing a  contraction  produced  by  "ergamine."  Adrenaline,  however,  caused  a 
marked  dilatation.  This  seems  to  indicate  definitely  that  benzyl  benzoate 
does  not  cause  a  bronchodilatation  in  intact  (pithed)  dogs  under  the  condi- 
tions obtaining  in  such  experiments  as  we  have  here  carried  out.  Fig.  11 
shows  three  separate  tracings  mounted  together.  From  the  legends  it  will 
be  seen  that  benzyl  benzoate  did  not  produce  satisfactory  bronchodilatation 
in  either  instance. 

The  possibility  that  benzyl  benzoate  might  be  used  clinically  in  pulmonary 
hemorrhage  in  cases  of  tuberculosis  led  us  to  investigate  the  action  of  the 
drug  on  the  pulmonary  blood  pressure.  The  method  we  have  used  for  re- 
cording the  pulmonary  arterial  pressure  is  indicated  in  Fig.  12.  (See  Jour. 
Lab.  and  Clin.  Med.,  1920,  vi,  1).  In  the  diagram  it  will  be  seen  that  a 
cannula  tied  into  the  left  pulmonary  artery  connects  with  a  water  mano- 
meter, the  distal  end  of  which  is  joined  to  the  lower  end  of  a  burette.  The 
manometer  and  tubes  to  the  artery  (and  the  cannula)  are  filled  with  normal 
salt  solution.  The  upper  end  of  the  burette  is  connected  with  a  recording 
tambour  which  writes  on  the  drum.  The  tambour,  the  upper  part  of  the 
burette  and  the  connecting  tubes  are  filled  with  air.  By  this  method  the 
pulmonary  blood  pressure  record  represents  a  magnification  about  150 
times  greater  than  would  be  recorded  by  a  mercury  manometer.  The  varia- 
tions in  the  pulmonary  tracings  should,  therefore,  be  reduced  about  150  times 
in  amplitude  in  order  to  compare  them  directly  with  the  associated  carotid 
tracings  which,  in  our  records,  were  made  with  a  mercury  manometer.  Fig. 
13  shows  the  results  we  have  observed  on  the  pulmonary  arterial  pressure. 
Near  the  beginning  of  the  tracing  3  cc.  of  benzyl  benzoate  was  injected  and 
a  typical,  prolonged  fall  in  the  carotid  pressure  was  obtained.  In  the  pul- 
monary pressure,  however,  there  was  produced  at  first  a  sharp  temporary 
rise  which  was  succeeded  by  a  few  gasping  movements.  But  on  the  average 
there  was  extremely  little  variation  in  the  pulmonary  pressure,  either  in  the 
way  of  a  rise  or  a  fall.  Later  a  3  cc.  injection  of  benzyl  benzoate  was  given 
again.  The  fall  produced  in  the  carotid  pressure  was  again  quite  typical, 
but  the  pulmonary  pressure  showed  only  a  very  slight,  transient  rise.  A 
small  injection  of  adrenaline  was  finally  given  in  order  to  check  up  the 
accuracy  of  the  technic  in  the  experiment.  Fig.  14  shows  two  short  pul- 
monary tracing  (mounted  together).  Here  again  the  drug  produced  only 
the  slightest  changes  in  the  pulmonary  pressure.  In  studying  these  tracings 
one  must,  of  course,  constantly  bear  in  mind  the  greatly  increased  magnifi- 
cation of  the  pulmonary  over  the  carotid  records.  It  is  obvious  that  if  the 
drug  should  act  in  clinical  cases  in  a  manner  at  all  analogous  to  that   in 


RANSOHOFF  MEMORIAL  VOLUME 

which  it  lias  behaved  under  these  experimental  conditions,  it  could  be  of 
no  use  in  the  matter  of  treatment  of  hemoptysis  in  puhnonary  tuberculosis. 

REFERENCES. 

1.  Maclit,   David  I.:    Jour,    Pharmacol,   and    Exper.    Thcrap.,    19IS.   xi,    No.    6,   p.   421. 

2.  Macht,  David  I.:    Jour.  Am.  Med.  Assn.,  August  23,  1919,  pp.  599-601. 

3.  Litzenhpre.  Jennings  C:     Jour.  Am.  Med.  Assn..  August  2.3,  1919,  pp.  6C1-603. 

4.  Macht.  David  J.:     .Southern  Med.  Jour.,  July,  1919,  xii.  No.  7,  p.  367. 


RELATION  OF  THE  DEVELOPMENT  OF  THE  GASTRO-  * 
INTESTINAL  TRACT  TO  ABDOMINAL  SURGERY.* 

W.  J.  Mavo,  M.  D. 

Rochester,  Minn. 

THE  RELATION  OF  ANATOMY  TO  PRESENT  DAY  SURGERY. 

The  late  Corydon  L.  Ford,  professor  of  anatomy  at  the  University  of 
Michigan  Medical  School,  was  justly  considered  the  greatest  teacher  of  anat- 
omy of  his  time.  I  well  remember  the  three  years  in  which  I  studied  anat- 
omy under  him,  and  the  impression  he  made  on  the  students  by  his  clear 
and  forceful  presentation  of  this  ordinarily  dry  subject.  He  was  then  a  man 
past  middle  life;  he  wore  a  beard,  shaved  the  upper  lip,  and  because  of  a 
congenital  clubfoot  he  walked  with  a  decided  limp  by  the  aid  of  an  ivory- 
headed  cane.  I  speak  of  these  physical  factors  because  they  were  part  and 
parcel  of  the  man  in  relation  to  his  teaching.  He  presented  anatomy  not 
alone  as  a  fundamental  science  which  it  was  necessary  to  master  for  the 
purpose  of  laying  a  foundation  for  clinical  medicine,  but  as  a  living  thing 
to  be  considered  in  almost  every  professional  act.  He  was  closely  in  touch 
with  the  clinical  issues  of  his  time,  and  with  anatomy  he  taught  most  valuable 
lessons  in  physiology  and  pathology,  so  that  the  student  gained  knowledge 
of  his  subject  in  its  relation  to  his  work.  The  university  courses  in  surgical 
anatomy  were  excellent,  yet  Ford  taught  us  more  surgical  anatomy  than 
we  learned  in  these  special  courses,  and  he  also  taught  us  medical  anatomy, 
in  order  that  we  might  see  the  patient  from  the  anatomic  standpoint,  and 
recognize  pathologic  deviations  from  the  normal  in  the  early  stages.  We 
were  drilled  in  the  use  of  Holden's  "Anatomical  Landmarks";  I  have  spent 
many  hours  with  this  little  book,  going  over  the  living  body  that  I  might 
learn  the  relation  of  the  external  to  the  internal. 

As  volunteer  assistant  I  had  the  further  privilege  of  demonstrating  anat- 
omy at  the  University  of  Michigan,  and  the  fascination  for  anatomic  detail 
in  relation  to  medicine  and  surgery  has  remained  with  me.  My  seat  com- 
panion was  the  late  Franklin  P.  Mall,  afterward  professor  of  anatomy  at 
Johns  Hopkins,  and  the  most  distinguished  anatomist  of  his  time.  Mall  was 
a  choice  spirit,  an  anatomist  of  the  research  type.  On  one  occasion  in  show- 
ing me  the  manner  in  which  the  heart,  by  its  peculiar  twisting  contraction, 
empties  all  the  blood  from  its  cavities  as  one  would  wring  a  cloth,  he  re- 
marked that  a  cavity  like  the  bladder  cannot  empty  itself  to  the  last  drop 
by  contractions  alone.  He  said  that  anatomy  since  Ford's  time  had  dealt  too 
much  with  abstract  matter.  Mall's  observation  has  an  important  bearing  on 
catheter  cystitis,  an  infection  of  a  small  amount  of  residual  urine  in  an 
overstretched  organ. 

•Mayo  Foundation  lecture,  given  before  tlie  University  of 
Medicine  and  tlie  Physicians'  and  Surgeons'  Club,  Rochester,  Minn. 
Journal  of  the  American  Medical   Association.    February.   1920. 


RANSOHOFF  MFMORIAL  VOLUME 


During  my  active  experience  in  surgery,  working  with  many  different 
assistants.  I  have  not  always  been  impressed  with  their  knowledge  of  anat- 
omy, although  all  have  possessed  a  fair  knowledge  of  pathology.  At  times 
it  would  seem  that  they  were  more  familiar  with  minute  pathology  than 
with  anatomy.  Microscopic  histology  and  pathology,  while  not  overdone, 
have  been  allowed  to  overshadow  anatomy  and  gross  pathology — these  the 
surgeon  or  internist  must  see  with  his  own  eyes  if  he  is  to  do  his  best  work. 
It  is  a  question  in  my  mind  whether,  generally  speaking,  anatomy  is  as  well 
taught  today  as  it  was  in  my  student  days ;  whether  it  is  taught  with  a  view 
of  instilling  in  a  man  a  love  for  the  subject,  or  merely  as  a  foundation  for 
medical  practice.  I  believe  this  tendency  is  correctly  interpreted  by  teaching 
anatomists  of  the  type  of  Jackson  and  others,  who  are  taking  steps  to 
remedy  the  existing  defects  by  the  better  balancing  of  anatomic  teaching. 
This  is  also  true  of  the  teaching  of  present  day  pathologists. 

In  surgery  of  the  abdomen  especially,  a  wide  knowledge  of  embryology 
and  anatomy  is  essential.  In  the  olden  time  when  operations  were  done  in 
late  periods  of  pathologic  conditions,  and  were  destructive  rather  than 
reconstructive  because  it  was  necessary  to  save  life  and  it  was  too  late  to 
save  function,  one  could  fully  appreciate  the  answer  of  the  distinguished 
surgeon  who  originated  excision  of  the  hip  when  asked  concerning  the  ana- 
tomic details  of  the  operation:  "Damn  the  anatomy;  stick  close  to  the 
bone."  Today  the  bulk  of  surgery  is  not  done  for  gross  defects  but  for 
pathologic  conditions  which  have  not  deviated  from  the  normal  to  such  an 
extent  that  destructive  surgery  is  necessary,  but  are  still  in  condition  for 
reconstruction.  It  has  been  said  that  the  anatomist  never  made  a  good  sur- 
geon :  that  it  was  the  pathologist  who  made  the  surgeon.  This  is  true  only 
of  the  vanishing  German  type.  The  surgeon  of  tomorrow  must  follow  in 
the  footsteps  of  such  men  as  Deaver ;  he  must  be  an  anatomist  and  a  physi- 
ologist, and  living  pathology  must  hold  a  greater  place  in  his  mind  than  the 
pathology  which  has  been  developed  from  the  mortuary  and  has  dominated 
medicine  for  the  past  generation. 

For  many  years  I  have  been  interested  in  elucidating  problems  of  sur- 
gery of  the  abdomen.  Clinical  diagnosis  has  been  notoriously  unreliable, 
and  the  postmortem  does  not  show  the  chronic  disease  from  which  the 
patient  was  sick  during  life,  but  rather  the  particular  complication  from 
which  he  died.  Always,  when  I  have  faced  a  new  problem  in  this  field.  I 
have  gone  back  to  embryology,  anatomy  and  physiolog>'  in  order  to  gain 
an  idea  of  the  meanings  of  those  pathologic  deviations  which  we  are  called 
on  to  treat.  It  may  not  be  out  of  place  at  this  time  to  outline  sketchily  some 
of  the  anatomic  and  physiologic  principles  that  have  grown  up  with  the 
surgery  of  the  abdomen,  and  on  which  depends  the  explanation  of  many 
phenomena  that  could  not  otherwise  be  understood. 

From  the  time  the  food  passes  through  the  pharynx  until  it  enters  the 
rectum  we  have  comparatively  little  control  over  it.  Some  control  is  exer- 
cised in  the  esophagus  and  even  in  the  fundus  of  the  stomach  so  that  by 


IV.  J.  MAYO 


initiating  retrograde  movements,  retching,  and  so  forth,  some  food  may 
be  ejected.  The  same  is  true  in  the  sigmoid ;  but  even  in  it  the  control  at 
best  is  but  partial  and  indirect.  The  biologists  have  pointed  out  that  the 
theory  of  the  three  blastodermic  membranes  is  a  working  rule  and  not  a 
law,  having  many  exceptions ;  but  at  least  it  leads  to  logical  thought.  To  a 
certain  extent  this  is  also  true  of  the  idea  of  the  derivation  of  the  gastro- 
intestinal tract  from  the  fore,  middle  and  hind  guts.  Yet  these  primitive 
derivatives,  while  not  as  exact  in  the  present  day  human  body  as  might  be 
desirable  from  a  purely  scientific  point  of  view,  have  great  value  as  outlines 
for  the  student. 

From  the  foregut  come  the  stomach,  the  duodenum  down  to  the  com- 
mon duct,  the  liver  and  the  pancreas,  all  organs  which  prepare  food  for 
digestion  but  do  not  themselves  absorb.  The  stomach  does  not  absorb  even 
water,  although  it  will  take  up  certain  chemicals  and  poisons,  alcohol,  for 
instance.  The  derivatives  of  the  hindgut  likewise  absorb  nothing  except 
certain  chemical  substances,  and  rectal  feeding,  as  spoken  of  in  its  ordinary 
sense,  does  not  exist :  it  is  simply  a  means  whereby  material  placed  in  the 
rectum  is  quickly  carried  by  what  Bond  calls  "mucous  currents"  back  into 
the  derivatives  of  the  midgut  for  absorption.  The  so-called  colon  tube  passes 
out  of  sight  through  the  anus,  coiling  in  the  rectum,  and  but  seldom  passes 
the  rectosigmoid  barrier.  The  derivatives  of  the  foregut  have  their  blood 
supply  from  the  celiac  axis.  The  derivatives  of  the  midgut,  in  which 
absorption  takes  place,  are  supplied  from  the  superior  mesenteric  artery, 
while  the  inferior  mesenteric  artery  supplies  the  derivatives  of  the  hindgut 
as  far  down  as  the  rectum,  and  very  largely  the  rectum  also,  although  the 
rectum  and  anal  canal  obtain  a  small  supply  from  the  middle  and  external 
hemorrhoidals  because  of  their  origin  from  the  cloaca  and  the  protodeum. 

Rosenow's  work  on  the  specificity  of  bacteria  shows  the  bacteria  that 
have  been  cultivated  in  certain  soils,  in  the  gallbladder,  for  example,  when 
placed  in  the  circulation,  are  peculiarly  attracted  to  the  organ  to  which  they 
have  been  acclimated.  That  is,  strains  of  bacteria  derived  experimentally 
from  a  gallbladder  will  more  often  set  up  a  cholecystitis  than  if  they  were 
derived  from  some  other  organ.  This  is  true  along  so  many  lines  connected 
with  the  vascular  system  that  we  must  admit  at  least  the  possibility  that  the 
blood  supply  is  to  a  certain  extent  specific  and  that  organs  exercise  some 
peculiar  chemotaxis  which  physiologically  and  pathologically  directs  cer- 
tain substances  of  the  blood  content  to  them.  How  else  can  we  explain  the 
rapidity  with  which  phenolsulphonephthalein  is  eliminated  through  the  kid- 
neys? And  recent  work  in  physics  suggests  that  the  attraction  may  be  a 
physico-chemical  one.  Very  delicate  instruments  appear  to  show  that  each 
organ  has  its  own  electrical  reactions  and  polarity,  suggesting  that  cancerous 
growths  can  be  recognized  in  this  way. 

Embryologically  the  first  portion  of  the  duodenum  ends,  not  at  the  py- 
lorus but  at  the  common  duct,  and  the  duodenum  above  the  common  duct 
embryologically  is  a  part  of  the  stomach  and  a  vestibule  to  the  small  intes- 


RANSOHOFF  MEMORIAL  VOLUME 


tine;  like  the  stomach  and  other  acid-containing  organs,  it  is  extremely 
liable  to  ulceration.  Ulcers  of  the  duodenum  occur  more  commonly  in  men 
than  in  women,  possibly  because  the  first  portion  of  the  duodenum  in  women 
is  more  nearly  horizontal,  naturally  permitting  of  a  higher  alkaline  level  for 
the  bile  and  pancreatic  juice,  and  thereby  reducing  the  liability  to  ulcera- 
tion. In  animals  with  bilocular  stomachs  the  division  between  the  two 
stomachs  is  at  the  incisura  of  the  human  stomach,  and  the  physiologic 
activity  of  the  pyloric  half  of  the  stomach,  especially  at  the  incisura,  is  quite 
evident  on  roentgen-ray  examination,  although  the  musculature  composing 
the  primitive  sphincter  has  disappeared. 

The  termination  of  the  absorbing  intestinal  area  in  the  transverse  colon 
near  the  splenic  flexure  embryologically  marks  the  end  of  the  absorbing  area. 
It  is  interesting  to  note  that,  although  the  proximal  half  of  the  large  intestine 
has  no  marked  anatomic  differences  from  the  left  half,  in  the  embryo  villi 
are  to  be  found  in  the  right  half  which  are  similar  to  the  villi  of  the  small 
intestine,  although  they  disappear  as  development  proceeds.  An  observer, 
watching  with  the  roentgen  ray  the  churning  back  and  forth  in  the  head  of 
the  colon  sees  that  the  greater  part  of  this  activity  is  proximal  to  the  loca- 
tion of  the  cecocolic  sphincter  which  exists  in  the  ascending  colon  of  some 
of  the  lower  animals,  and  that  physiologic  contractions  are  most  marked  in 
this  situation.  Retardation  of  the  passage  of  food  through  the  intestinal 
tract  has  its  origin  in  embryologic  physiology.  Muscular  control  by  means 
of  sphincters,  delay  by  means  of  the  valvulae  conniventes  which  also  pre- 
sent larger  exposed  surfaces  for  absorption,  delay  by  sacculations,  as  in  the 
large  intestine,  and  mechanical  delays,  such  as  the  high  attachments  of  the 
splenic  flexure  which  necessitate  muscular  activity  in  order  to  pass  the  food 
refuse  into  the  nonabsorbing  part  of  the  large  intestine  and  render  the 
descending  colon  physiologically  empty,  are  examples.  The  rectosigmoid 
is  a  most  remarkable  mechanical  device  for  retardation  of  food  end-prod- 
ucts. Since  nature  is  most  sparing  of  waste,  even  of  water,  in  the  terminal 
half  of  the  large  intestine,  especially  the  sigmoid,  the  fluids  are  gradually 
squeezed  out  of  the  refuse  and  passed  by  reverse  currents  back  into  the 
proximal  half  of  the  colon  for  absorption. 

Rotation  has  great  surgical  significance.  In  the  embryo  and  in  many 
lower  animals  throughout  life  the  stomach  hangs  with  its  lesser  curvature 
facing  ventrally;  and  embryologically  the  lesser  curvature  is  the  anterior 
wall  of  the  stomach.  Rotation  turns  the  stomach  and  pancreas  on  their 
right  sides.  The  pancreas,  embrylogically  an  intraperitoneal  organ,  loses 
its  posterior  layer  of  peritoneum,  which  becomes  fused  behind  with  the 
fascia.  This  explains  why,  in  the  type  of  acute  pancreatitis  and  fat  necro- 
sis which  might  be  picturesquely  called  "perforation,"  the  pancreas  may 
involve  the  fat  behind  the  peritoneum  as  well  as  the  intra-abdominal  fat; 
why  occasionally,  in  traumatism,  pancreatic  secretions  escaping  into  the 
lesser  cavity  of  the  peritoneum  may  penetrate  into  the  omentum  and  form 
a  collection  of  fluid  in  what  is  known  as  the  omental  bursa,  reopening  the 

Page  S9^ 


W.  J.  MAYO 


cavity  which  in  fetal  life  exists  between  the  layers  of  the  omentum  before 
tliey  are  fused  as  high  as  the  transverse  colon. 

The  position  of  the  duodenum  is  altered  by  rotation  and  its  third  portion 
becomes  retroperitoneal,  a  fact  of  great  importance  in  connection  with 
operations  on  the  right  kidney.  Unless  care  is  exercised  in  performing  a 
nephrectomy  in  cases  in  which  there  is  chronic  inflammation  around  the 
pelvis,  and  especially  in  malignant  disease,  the  duodenum  may  be  injured, 
and  immediately  or  a  few  days  later  a  fistula  form  from  which  the  patient 
may  die  unless  it  is  repaired  anteriorly  by  a  transperitoneal  operation.  Very 
scanty  mention  of  this  accident  is  found  in  the  literature,  but  I  have  reported 
several  cases  of  this  character.  Unless  careful  dissection  is  made,  this 
retroperitoneal  portion  of  the  duodenum  also  may  be  injured  in  the  removal 
of  cancers  of  the  ascending  colon. 

Rotation  as  it  affects  the  intestinal  tract  is  also  of  great  surgical  impor- 
tance. The  large  intestine,  having  its  origin  on  the  left  side  of  the  body, 
passes  to  the  right  and  does  not  reach  its  normal  situation  until  after  birth. 
The  late  peritoneal  attachments  are  often  described  as  veils  or  adhesions, 
and  are  given  unwarranted  credit  for  causing  trouble.  Failure  of  rotation 
or  partial  rotation  will  cause  the  physical  signs  of  an  appendicitis  to  appear 
at  whatever  point  the  rotation  of  the  head  of  the  colon  is  interrupted.  The 
attachments  of  the  large  intestine  to  the  right  side  are  not  only  late  and  less 
close  than  those  on  the  left,  but  also,  since  the  cubic  capacity  of  the  right 
lower  thorax  is  less  than  that  of  the  left  lower  thorax,  because  of  the  liver, 
the  right  kidney  normally  lies  lower  than  the  left.  The  nephrocolic  liga- 
ment may  be  called  on  to  bear  much  of  the  weight  of  the  head  of  the  imper- 
fectly attached  colon  which  acts  like  the  car  attached  to  a  balloon,  and  may, 
by  traction,  drag  the  kidney  down.  We  think  of  the  large  intestine  as  having 
a  short  mesentery ;  but  as  a  matter  of  fact,  it  has  a  very  long  mesentery  on 
the  inner  side,  which  is  the  only  side  of  importance,  as  the  blood  vessels, 
lymphatics  and  nerve  supply  are  always  to  be  found  in  the  inner  long  leaf 
which  follows  the  colon  during  its  migration.  The  outer  peritoneal  attach- 
ments which  hold  the  colon  in  place  laterally  may,  therefore,  be  divided  with- 
out encountering  any  structures  of  importance,  and  the  large  intestine,  on 
its  long  inner  leaf  of  mesentery,  can  be  drawn  out  of  the  body  for  easy 
manipulation  and  operation.  There  is  one  exception;  that  is,  the  attach- 
ments of  the  splenic  flexure  are  derived  from  the  omentum  and  contain  a 
blood  vessel  which  must  be  tied.  Some  years  ago  I  called  attention  to  this 
method  of  mobilizing  the  large  intestine,  which  is  based  on  these  anatomic 
facts  and  very  greatly  aids  in  operations  on  the  colon. 

The  small  intestine,  originating  in  six  primary  convolutions  on  the  right 
side,  has  its  mesenteric  attachment  from  left  to  right,  from  above  down- 
ward, passing  behind  the  umbilicus.  This  is  the  reason  why  in  obstructive 
and  other  disturbances  of  the  small  intestine,  unless  localized  by  involve- 
ment of  the  peritoneum,  the  pain  is  referred  to  the  vicinity  of  the  umbilicus, 
although  the  cause  of  the  pain  may  be  in  a  loop  of  intestine  at  a  distance. 

Page  39$ 


RANSOHOFF  MEMORIAL  VOLUME 


In  picking  up  a  loop  of  small  intestine,  it  is  sometimes  difficult  to  determine 
which  direction  is  up  and  which  is  down.  Monks,  in  a  beautiful  piece  of 
work,  has  shown  how  this  can  be  done  with  facility.  If  a  loop  of  intestine 
drawn  out  of  an  abdominal  incision  is  held  by  an  assistant,  and  the  surgeon, 
grasping  the  intestine  with  the  fingers  on  one  side  and  with  the  tliumb  on 
the  other,  passes  down  to  the  bottom  of  the  mesentery,  and  finds  that  his 
fingers  and  thumb  still  grasp  the  root  of  the  mesentery  as  started  above,  the 
direction  is  up  and  down ;  but  if  the  position  is  reversed  at  the  base,  then  the 
direction  is  the  opposite.  In  picking  up  a  piece  of  small  intestine  one  should 
be  able  to  recognize  the  part  of  the  bowel  from  its  appearance.  The  upper 
jejunum  is  thick  and  wide,  the  mesentery  is  thin,  and  the  vessels  are  large, 
long  and  straight,  having  but  one  or  two  primary  arcades  close  to  the  base. 
In  the  lower  ileum  the  intestine  is  thin  and  the  mesentery  thick,  the  fat  some- 
times following  the  vessels  a  little  way  up  along  the  intestinal  wall.  The 
vessels  are  smaller,  shorter,  and  there  are  a  number  of  arcades,  sometimes 
two,  three  or  four,  in  the  adjacent  mesentery.  Attention  to  these  details 
makes  ready  differentiation  possible. 

The  study  of  the  peritoneum  is  profitable  to  the  surgeon.  The  resistance 
of  the  peritoneum  to  infection  is  an  inherited  faculty.  The  meninges  and 
pleura  have  less  resistance.  In  the  earthworm  (common  angleworm),  the 
food,  in  its  jirogress  through  the  primitive  gastro-intestinal  canal,  is  admitted 
into  the  coelom,  or  body  cavity,  which  is  the  forerunner  of  the  peritoneum, 
for  direct  absorption.  The  contaminated  peritoneum  liefore  infection  takes 
place  usually  needs  no  drainage  after  mechanical  cleansing;  drainage  often 
does  harm  rather  than  good.  The  slowly  acquired  special  resistance  of  the 
pelvic  peritoneum  of  women  to  infections  in  the  course  of  countless  genera- 
tions of  sulTfering  from  puerperal  and  other  infections,  is  well  known;  and 
the  mortality  rate  of  operations  involving  the  pelvic  peritoneum,  such  as 
resections  of  the  rectum  for  cancer,  is  much  less  in  women  than  in  men. 

Let  me  repeat  that  the  teaching  of  anatomy,  as  related  to  constructive 
surgery  rather  than  to  the  destructive  surgery  of  the  past,  should  be  based 
on  the  needs  of  the  surgeon  of  today,  to  enable  him  to  cope  with  the  diseases 
of  today.  If  I  were  to  write  a  book  (I  have  no  intention  of  inflicting  one  on 
the  medical  public),  I  should  take  up  the  fascinating  story  of  embryology, 
anatomy  and  ])hysiology  in  relation  to  the  work  of  the  surgeon  of  tomorrow, 
the  story  of  the  anatomy  of  the  living  to  enable  us  to  treat  the  i)athology  of 
the  living  during  the  early  stage  of  deviation  from  the  normal  physiologic 
state. 

CO-ORI^IXATIO\    OF    THE    FUN'CTIOXS    OF    THE    OASTRO-IXTESTIN'.AL 
TR.^CT 

The  two  most  primitive  functions  of  a  living  body  are  maintenance  of 
nutrition  and  reproduction,  and  nature  has  thrown  about  these  functions  the 
greatest  possible  number  of  safeguards.  First,  the  body  must  be  nourished, 
and  second,  new  life  is  to  be  brought  into  being.     This  is  as  true  of  the 

Page  aim 


W.  J.  MAYO 


simple  cell  as  of  the  most  complex  organism.  The  more  ancient  the  organ, 
the  greater  its  resistance.  The  small  intestine  has  an  enormous  resistance 
to  disease  and  seldom  is  the  seat  of  neoplasm.  The  testicle,  which  is  the 
primitive  rei)rodnctive  organ,  has  a  long  heredity  and  freedom  from  disease. 
On  the  contrary,  the  ovary,  which  is  descended  from  the  testicle,  is.  like 
other  less  ancient  organs,  such  as  the  stomach,  the  rectum  and  the  large 
intestine,  a  frequent  seat  of  neoplasm. 

Methods  of  ciMitrol  over  the  visceral  functions  were  established  before 
man  had  a  central  nervous  system;  the.se  controls  are  still  independent  of 
it.  It  might  even  be  surmised  that  the  attempt  of  the  central  nervous  system 
to  gain  control  over  visceral  and  other  functions  previously  established  may 
have  to  do  with  neurasthenia,  especially  its  visceral  manifestations.  Starling 
well  says  that  those  internal  secretions,  which  he  calls  hormones,  precede  all 
types  of  nervous  systems  in  visceral  control.  One  is  perhaps  justified  in 
looking  on  the  sympathetic  as  the  more  primitive  nervous  system  and  in  be- 
lieving that  the  means  whereby  the  central  nervous  system  is  attempting  to 
gain  this  control  over  the  vegetative  functions  is  through  the  autonomic 
nervous  system. 

The  liver,  entirely  separated  from  all  its  connections,  can  be  made  to 
secrete  bile,  and  the  kidney  similarly  to  secrete  urine.  For  that  matter,  the 
entire  viscera  have  been  completely  separated  experimentally  from  the  nerv- 
ous system  and  even  lifted  out  of  the  body,  and  by  appropriate  mechanical 
connections  made  to  live  and  function  for  some  hours.  The  central  nervous 
system,  we  find,  has  more  or  less  control  of  those  organs  which  have  been 
added  more  recently,  especially  organs  of  convenience,  such  as  the  fundus  of 
the  stomach,  into  which  a  quantity  of  food  may  be  placed  rapidly  for  elabo- 
ration, as  the  magazine  of  a  coal  stove  may  be  filled.  The  sigmoid  and  the 
bladder  also  have  temporary  storage  function  ;  but  in  other  resjjects  the  cen- 
tral nervous  system,  bevond  initiating  action,  plavs  a  small  ]3art  in  \'egetative 
life. 

The  growth  of  the  central  nervous  svstem  in  relation  to  the  organs  of 
special  sense  is  interesting.  First,  the  sense  of  taste,  which  made  the  selec- 
tion of  food  possible ;  second,  the  sense  of  smell,  which  enabled  the  primi- 
tive stoma  to  be  turned  toward  food,  and  third,  the  sense  of  hearing,  which 
was  placed  in  the  middle  of  the  head  because  danger  threatens  from  behind 
as  well  as  in  front.  The  sense  of  sight  came  during  the  rapid  development 
of  all  the  higher  cerebral  faculties,  and  direct  pathways  were  established 
between  the  eye  and  all  parts  of  the  brain,  so  that  the  sense  of  sight  over- 
shadows in  importance  the  other  special  senses.  Even  memory  in  most 
persons  has  its  basis  in  visual  phenomena.  The  relatively  short  heredity 
of   the   central   nervous   .system   accounts    for   its   instability. 

It  is  interesting  to  note  that  the  sympathetic  nervous  system  is  in  close 
relation  with  the  endocrine  glands,  and  that  the  importance  of  the  internal 
secretion  of  an  organ  may  be  estimated  by  the  closeness  of  its  relation  to 


RANSOM  OFF  MEMORIAL  VOLUME 


the  sympathetic  system.  The  pituitary,  one-half  sympathetic  and  one-half 
gland,  the  suprarenal,  with  its  similar  association,  and  the  thyroid,  are  ex- 
amples; the  spleen  has  no  internal  secretion  of  great  importance,  and  only 
small  connection  with  the  s_\anpathetic  system. 

Still  another  form  of  control  is  found  in  the  primitive  character  of  the 
nonstriated  muscle.  These  fibers  have  the  power  of  originating  motion 
independent  of  a  known  nervous  system.  A  little  piece  of  the  wall  of  the 
small  intestine  will  contract  for  hours  when  placed  in  Locke's  solution  and 
properly  stinnilated.  Many  visceral  functions  are  dependent  on  the  non- 
striated  muscle.  We  are  indebted  to  Keith  for  revelations  with  regard  to 
the  curious  nodal  system  which  acts  to  collect  the  impulses  that  have  their 
origin  in  the  primitive  fibers  of  the  nonstriated  muscle.  This  has  been  most 
carefully  studied  with  reference  to  the  heart.  The  heart-beat  starts  in  the 
sinu-auricular  node,  is  diffused  through  the  auricular  musculature,  and  is 
passed  by  the  muscle-band  of  His  to  the  vetricles,  timing  the  ventricular 
beat.  Keith's  nodes  are  composed  of  a  curious  type  of  primitive  muscle- 
cell  with  some  fine  fibers  from  the  autonomic  nervous  system  which  evi- 
dently were  added  later.  These  nodes  are  in  eflfect  the  controlling  ganglions 
of  the  action  of  the  nonstriated  muscle  in  organs.  Keith  has  pointed  out 
the  situation  of  eight  nodes,  four  located  and  four  not  fully  identified, 
througli  which  control  is  maintained.  When  food  passes  through  the 
pharynx,  all  direct  control  is  at  once  lost,  and  here  is  situated  the  first  node. 
The  cardia  is  a  true  sphincter  and  normally  is  closed.  The  food  passing 
through  the  esophagus  arouses  contractions  in  the  nonstriated  muscle  of 
the  esophagus ;  these  impulses  are  carried  to  the  second  node,  which  relaxes 
the  cardiac  orifice.  Failure  to  relax  the  cardiac  orifice  results  in  that  curi- 
ous condition  called  cardiospasm  from  which  many  persons  suffer  and 
starve  for  years,  and  often  die  from  obstruction  sujiposed  to  be  due  to  can- 
cer. If  we  have  knowledge  of  the  nature  of  the  diseasf.  cure  is  easy  ;ind 
certain.  The  third  node  is  not  at  the  pylorus  as  one  wduld  think,  but  at 
the  termination  of  the  primitive  foregut  near  the  common  duct.  It  is  in- 
teresting to  note  that,  as  pointed  out  by  Ochsner,  there  are  remnants  of  a 
prehistoric  sphincter  at  this  point.  Disturbances  of  this  node  produce  the 
condition  called  pylorospasm,  which  accounts  for  many  gastric  disturbances 
masquerading  under  dififerent  names.  This  node  is  also  concerned  in 
chronic  gastric  atony  and  some  of  the  phases  of  acute  dilatation  of  the 
stomach.  The  fourth  node  is  near  the  duodenojejunal  juncture  and  is  con- 
cerned normally  in  peristalsis  and  in  segmentation  or  pendulum  movements 
of  the  small  intestine,  and  abnormally  in  producing  gastromesenteric  ileus. 
The  fifth  node  is  at  the  ileocecal  juncture  and  is  concerned  with  many  of 
those  phenomena  about  which  Lane  has  written  so  interestingly  under  the 
general  head  of  ileac  stasis.  The  sixth  node  is  near  the  middle  of  the  trans- 
verse colon,  and  through  its  control  of  antiperistalsis  prolongs  the  reten- 
tion of  food  products  for  absorption  in  the  right  half  of  the  colon.     The 

Page  S9i 


W.  J.  MAYO 


seventh  node  is  in  the  rectosigmoid  region,  and  disturbances  in  the  function 
of  this  node  are  probably  responsible  for  the  giant  colon  of  Hirschsprung's 
disease.     The  last,  or  eighth,  node  is  concerned  with  rectal  control. 

It  ma\'  be  said  that  wherever  nonstriated  muscle  exists,  the  power  of 
originating  contraction  exists.  The  intestine,  like  the  heart,  has  two  beats. 
The  first,  called  the  peristalsis,  beats  once  or  twice  to  the  minute.  The 
second,  as  pointed  out  by  Mall,  is  the  heart  of  the  portal  circulation  and 
beats  from  eighteen  to  twenty  times  a  minute,  forcing  the  blood  to  the 
liver.  In  the  pregnant  uterus,  the  beat  of  the  nonstriated  muscle  is  recog- 
nized as  the  uterine  contractions  of  pregnancy.  Keith  points  out  the  part 
played  by  the  nodes  in  controlling  peristalsis,  and  suggests  that  they  act 
like  a  block  system  on  a  railroad,  and  control  food  progress  by  controlling 
sphincters. 

The  endocrine  glands  secrete  substances  which  Starling  has  called  hor- 
mones; they  act  through  the  blood  stream  and  form  a  most  interesting 
chapter  in  visceral  control ;  they  are  closely  allied  to  the  sympathetic  nerv- 
ous system,  and  are  often  found  in  glands  of  double  function  or  glands 
that  at  one  time  have  had  an  external  as  well  as  an  internal  secretion.  The 
gonadial  secretion  derived  from  the  interstitial  cells  of  the  generative  or- 
gans controls  sex  characteristic  even  when  the  genital  elements  are  absent. 
The  relation  of  the  external  pancreatic  secretion  dealing  with  the  digestion 
of  fats,  starches  and  proteins  has  only  an  indirect  connection  with  the 
tissue  of  Langerhans,  which  has  to  do  with  sugar  metabolism.  The  thyroid 
in  the  king  scorpion  is  a  reproductive  gland,  and  the  thyroid  function  in 
the  human  being  is  closely  connected  with  puberty,  in  the  female,  with  the 
pregnant  state.  Types  of  life  are  found  in  which  the  thyroid  functioned 
through  the  digestive  tract,  and  the  foramen  cecum  at  the  base  of  the 
tongue  in  man  marks  the  site  where  this  secretion  was  at  one  time  discharged 
into  the  intestinal  canal.  In  the  present  stage  of  human  development,  the 
thyroid  is  entirely  an  organ  of  internal  secretion ;  Init  through  its  influence 
on  other  endocrine  glands,  it  assists  in  maintaining  reproductive  and  diges- 
tive functions. 

The  pituitary  gland  probably  corresponds  to  the  strainer  gland  in  the 
fish  stage,  and  in  the  course  of  development  was  left  within  the  skull  in- 
stead of  on  the  side  of  the  pharynx.  It  contains  elements  derived  from  the 
pharyngeal  mucosa,  and  many  of  its  tumors  show  pharyngeal  heredity.  Is  it 
possible  that  this  gland,  which  is  so  important  in  the  growth  of  the  body,  is 
favorably  affected  through  improved  circulation  by  the  removal  of  diseased 
adenoids  and  tonsils?  Certainly  one  often  sees  a  child  of  slow  development, 
after  an  operation  for  removal  of  tonsils  and  adenoids,  make  a  most  striking 
physical  and  mental  gain.  The  coccygeal  body  (gland  of  Luschka)  has  no 
known  function,  but  it  is  connected  with  that  stage  of  development  in  which 
the  primitive  hind  or  tail  gut  was  part  of  the  neurenteric  canal.  These  pre- 
natal vestiges  may  be  the  source  of  dermoids  or  neoplasms  of  peculiar  na- 

Page  399 


RANSOHOFF  MEMORIAL  VOLUME 


ture,  not  infrequently  malignant,  lying  in  the  hollow  of  the  sacrum  behind 
tl^e  rectum  and  eroding  the  bone.  Some  theorists  have  called  the  external 
xe^titrial  remnants  of  the  neurenteric  canal  the  posterior  umbilicus,  and  be- 
licxe  that  tiie  sequestration  dermoids  so  frequently  found  in  the  lower  sacral 
and  coccygeal  midline  have  this  origin.  Keith  points  out  that  the  interna! 
secretions  of  the  five  important  endocrine  glands:  pituitary,  suprarenals, 
gonadial,  pineal  and  thyroid,  control  racial  characteristics  of  the  three  great 
divisions  of  man,  Caucasion,  Negro  and  Mongol. 

The  sympathetic  nervous  system  was  a  later  develoiJment,  and  correlates 
visceral  action.  It  stimulates  the  function  of  endocrine  glands,  and  is  in 
turn  stimulated  by  their  secretions.  To  the  great  English  physiologist  Gas- 
kell  we  owe  our  knowledge  of  the  involuntary  nervous  system.  His  first 
work  on  the  visceral  nervous  system  was  published  in  the  early  eighties. 
Gaskell  pointed  out  that  certain  small-calibered  medullated  nerves  pass  from 
the  anterior  horns  of  the  spinal  cord  to  the  great  sympathetic  ganglion  of 
the  thorax  and  abdomen,  which  connects  the  central  nervous  system  with 
llie  sympathetic.  These  connecting  nerves  enable  emotions  originating  in 
the  central  nervous  system  to  influence  the  sympathetic  ganglion.  From  the 
synt|)atbetic  ganglion  small  nonmedullated  fibers  pass  directly  to  their  dis- 
tribution forming  the  sympathetic  nervous  system.  Gaskell  also  showed 
that  there  are  nerves  of  the  same  kind  which  have  visceral  functions  arising 
from  the  cranial  nerves,  and  he  called  these  para-.sympathetics.  They  are 
composed  of  the  vagus  nerve,  the  fibers  in  the  third,  seventh  and  ninth 
cranial  nerves,  and  the  pelvic  nerve  from  the  sacral  plexus.  The  para- 
symiiatlictics  are  small-calibered  medullated  nerves  with  ganglion  cells  near 
their  distribution,  as  in  the  heart  itself  and  in  the  plexuses  of  Auerbach  in 
the  wall  of  the  intestine.  Neither  the  sympathetics  nor  the  parasympathetics 
are  under  the  control  of  the  will,  and  when  distributed  to  the  same  organ 
they  follow  Sherrington's  law  in  that  they  are  antagonistic. 

Langley,  who  contributed  much  to  this  work,  called  the  combined  sympa- 
thetic nervous  system  (thoracic  and  lumbar  ganglions)  and  the  parasympa- 
thetic (cranial  and  pelvic)  the  autonomic  system.  American  physiologists, 
especially  Cannon  and  Crile,  have  contributed  largely  to  this  work.  Gaskell 
pointed  out  that  the  symjiathetic  ganglions  develop  widespread  reactions 
to  slinnili  which  exercise  inhibitory  control  over  the  vegetation  system  inde- 
pendent of  the  will,  and  inhibit  the  parasympathetics.  The  cerebrospinal 
nervous  system  produces  a  conscious  and  accurate  action  of  the  striated 
muscle  system,  but  has  no  control,  and  only  indirect  effect,  on  the  non- 
striated  muscles.  Langley.  Crile,  Cannon  and  Brown  have  made  practical 
application  of  Gaskell's  discoveries,  showing  how  the  fibers  derived  from 
the  sympathetic  ganglions,  acting  for  defense,  produce  the  most  widespread 
and  sudden  effect  when  excited  by  emotions  such  as  fear  or  anger.  The 
digestive  tract  is  teni])orarily  (lepri\cd  of  function  ;  the  heart  action  and 
resjjiration   increase  in   rapidity  and  strength,  the  glands  of   internal  secre- 


W.  J.  MAYO 


tion,  especially  the  suprarenals  and  thyroid,  are  activated,  and  sugar  reserves 
in  tlie  liver  and  body  generally  are  thrown  into  the  blood  stream  to  enable 
greater  muscular  action. 

It  is  interesting  to  note  that  the  nerves  of  Gaskell  from  the  anterior 
horns  of  the  spinal  cord  to  the  sympathetic  ganglions  are  direct,  and  it  is 
only  those  nerve  fibers  derived  from  the  sym])athetic  ganglions  themselves 
that  pass  to  the  various  organs  to  produce  the  widespread  effects  spoken  of, 
with  the  exception  of  the  suprarenal  gland,  which  receives  fibers  from  the 
cord  en  route.  The  suprarenal  contains  within  itself  true  nerve  cells,  as 
though  at  one  time  a  start  had  been  made  for  a  dififerent  type  of  control 
from  that  which  was  afterward  developed  through  the  sympathetic  gan- 
glions. 'I'he  parasympathetics  of  Gaskell,  as  related  to  the  gastro-intestinal 
viscera,  are  composed  of  the  vagus  nerve  derived  from  the  bulbar  division 
of  the  parasympathetics,  and  the  pelvic  nerve  from  the  sacral  plexus.  When 
the  emotions,  which,  acting  through  the  sympathetic  system  cause  the  sud- 
den necessity  for  instantaneous  use  of  all  the  body  reserves,  have  passed 
away,  the  vagus  nerve  comes  into  action  and  causes  the  heart  to  beat  more 
slowly,  and  reduces  respiration.  The  digestive  tract,  the  stomach,  intestine, 
liver  and  pancreas,  which  have  been  temporarily  inhibited  by  the  sympa- 
thetic fibers  from  the  solar  plexus,  are  stimulated  to  function  through  the 
vagus  parasympathetic  acting  as  a  motor  nerve  through  the  plexus  of  Auer- 
bach,  and  the  pelvic  parasympathetic  motor  nerve  again  permits  conscious 
control  of  the  bladder,  sigmoid  and  rectum,  which  had  been  inhibited  by  the 
sympathetic  fibers  from  the  inferior  mesenteric  ganglion.  One  may  well  be- 
lieve, however,  that  while  these  functions  are  checked  by  the  sympathetic 
and  are  caused  to  resume  action  by  the  parasympathetics,  control  of  their 
normal  activities  goes  back  to  the  nonstriated  muscles,  and  the  internal  secre- 
tions which  were  the  earliest  forms  of  control.  The  gastro-intestinal  tract 
is,  therefore,  largely  controlled  in  its  functions  by  the  nonstriated  muscle 
and  by  chemical  substances  acting  through  the  blood.  The  sympathetic  gan- 
glions act  to  inhibit  these  functions  temporarily  to  produce  rapid  catabolism 
and  spend  reserves  prodigally.  The  parasympathetics  set  in  motion  the  in- 
terrupted anabolic  activities  and  maintain  reserves  for  future  emergencies. 

It  may  seem  that  these  well-known  anatomic  and  physiologic  details  need 
no  reiteration,  and  yet  in  my  association  and  teaching  of  younger  men  in 
the  profession  I  find  that  while  they  may  know  these  facts,  they  often  fail 
in  their  interpretation  of  them.  The  interpretation  of  the  interesting  phe- 
nomena which  I  have  cited  may  not  be  correct  in  given  instances;  but  if  by 
"near-right"  theories  a  dry  subject  may  be  made  to  live,  the  means  will  be 
justified  and  the  strain  on  our  memories  will  be  less.  We  must  not  forget 
that  memory  training  is  the  Confucian  method  which  certainly  has  not  led 
the  Chinese  in  the  ])aths  of  progress.  Facts  do  not  change.  The  interpreta- 
tion of  fads  constantly  changes,  and  new  interpretations  of  old  and  new 
facts  are  the  source  of  ])rogress.  (  )nly  as  we  are  doubtful  of  our  interpreta- 
tions can  we  hope  to  advance  scientifically. 

Papv    ',01 


THE  NECESSITY  FOR  THE  APPLICATION  OF  DIFFERENTIAL 
AIR-PRESSURE   IN  THORACIC   OPERATIONS.* 

W'ti.ly  Meyrr,  M.  D. 
New  York. 

For  the  second  lime  tlie  aniuial  meeting  brings  together  tlie  members 
of  tlie  American  Association  for  Tlioracic  Surgery. 

This  young  organization,  embracing  members  of  the  medical  profes- 
sion who  are  interested  in  the  study  of  diseases  of  organs  situated  within 
the  chest,  saw  the  light  of  day  at  the  time  of  the  meeting  of  the  American 
Medical  Association  in  New  York  City,  on  June  9,  1917,  and  celebrated 
its  first  birthday  in  Chicago  on  June  9,  1918. 

It  would  be  difficult  to  begin  this  second  meeting  better  than  by  re- 
peating the  words  with  which  the  first,  amidst  a  rising  vote  of  thanks,  was 
closed:  "Our  Association  is  proud  and  gratified  to  have  it  spread  on  its 
minutes  that  Dr.  S.  J.  Meltzer,  the  renowned  ])hysiologist  and  internist, 
the  man  who  has  done  so  nuich  for  the  evolution  of  thoracic  surgery,  was 
its  first  president." 

If  I  might  speak  my  inmost  thoughts,  I  would  say,  I  should  have  felt 
happy  had  there  been  no  successor,  and  had  Dr.  Meltzer  adorned  the  presi- 
dential chair  for  another  year,  nay,  for  life.  But  he  willed  it  otherwise ; 
and  so,  gentlemen,  by  your  kind  choice,  I  stand  before  you  as  your  pre- 
siding officer.  Let  me  thank  you  most  sincerely  for  the  honor  and  your 
trust ;  they  are  highly  appreciated. 

The  task  of  finding  a  topic  for  the  time-honored  presidential  address 
has  been  made  easy.  Within  the  last  year  we  have  had  new  proof  that 
the  usefulness  of  what  I  consider  the  very  foundation  of  modern  thoracic 
surgery,  viz.,  the  principle  of  employing  "differential  air-pressure"  in  the 
course  of  our  operative  work  within  the  thorax,  has  not  yet  been  generally 
recognized  in  its  importance  as  a  life-saver. 

Hence,  it  appears  to  me  appropriate  that  I  should  devote  this  address 
to  a  discussion  of  the  place  occupied  in  thoracic  surgery  by  differential 
pressure  apparatus,  using  the  words  in  their  widest  sense,  i.  e.,  including 
all  such  apparatus  and  methods  as  we  know  of.  In  again  calling  attention 
to  the  necessity  of  their  use  in  thoracic  operations,  I  feel  certain  to  be 
voicing  not  only  my  own  personal  opinion,  but  to  be  putting  on  record  the 
sense  of  the  majority  of  surgeons  in  this  Association. 

Let  us  see  just  what  does  occur  when  a  healthy  parietal  pleura  is  per- 
forated. \Miich  are  the  symptoms  and  sequelae  of  the  acute  pneumo- 
thorax?    Whicii  are  the  ]>liysical  and  pathological  conditions  surrounding  it. 


Copyright.   William   Wood  &   Company. 


JVILLY  MEYER 


"Observing  a  deeply  narcotized  dog,  whose  pleura  has  been  incised  in 
experimental  surgery,  a  very  typical  and  characteristic  clinical  picture  will 
be  seen  to  develop.  Immediately  after  the  opening  of  the  pleural  cavity 
and  the  subsequent  prompt  retraction  of  the  lung,  a  brief  cessation  of  the 
respiration  occurs  by  reflex.  This  is  followed  by  sudden,  almost  projectile 
attempts  at  inspiration  and  expiration.  The  entire  accessory  muscular  ap- 
paratus is  called  into  strenuous  action.  The  thorax  moves  up  and  down 
over  the  collapsed  lung  which  is  seen  lying  immovable  in  the  depth ;  its 
originally  glistening  surface  has  assumed  a  congested  appearance,  and  its 
normal  pinkish  color  has  given  way  to  a  dark  grayish-red.  Soon  the  fre- 
quency and  the  depth  of  the  respiration  increase,  as  may  be  observed  by 
watching  the  excursions  of  the  chest  wall.  At  the  same  time  the  respiration 
becomes  irregular.  After  a  few  minutes  the  symptoms  are  less  stormy, 
the  respiration  becomes  quieter  and  more  regular,  but  slower  and  dee]5er 
than  under  normal  conditions.  This  slowing  up  of  the  respiration,  which 
gradually  increases,  is  produced  by  the  lengthening  of  the  expiratory  phase. 
A  little  later  only  brief  inspirations  occur  at  longer  intervals.  Soon  the 
respiration,  and  therewith,  the  heart's  action  stop  completely.''  (Sauer- 
bruch.) 

Experiments  further  show  that  when  both  pleural  cavities  of  the  dog 
;irc  simultaneously  opened,  respiration  soon  ceases,  subsequent  to  most  vio- 
lent efforts  of  nature  to  hold  back  the  waning  life  by  means  of  very  deep 
ins])irations  and  expirations.     Death  occurs  by  suffocation. 

In  unilateral  acute  pneumothorax  in  the  human  subject,  the  disturb- 
ance is  frequently  less  pronounced  than  in  the  dog,  though  it  varies  widely 
in  severity  in  different  individuals. 

For  the  alteration  in  respiration  various  causes  are   responsible. 

Tiie  principal  role  is  played  by  the  mediastinum.  The  anatomical  or- 
gans and  parts  composing  the  mediastinum  divide  the  thorax  into  two  com- 
partments, which  latter  are  completely  filled  with  lung.  With  the  exception 
of  the  heart  and  large  blood  vessels  the  greater  part  of  the  mediastinal 
tissues  represent  a  soft  yielding  mass,  in  which  very  little  resistance  tu 
lateral  pressure  is  off'ered. 

Under  physiological  conditions  the  perfect  equality  of  forces  existing 
in  the  chest  on  both  sides  of  the  mediastinum  keep  the  contents  of  tlvj 
latter  in  their  normal  position  of  rest.  The  part  of  the  pleural  sac  that 
lines  the  mediastinal  structures,  chest  wall,  and  diaphragm — mediastinal, 
costal  and  diaphragmatic  pleura — is  in  close  approximation  with  the  other 
portion  of  the  pleural  sac  that  lines  the  lung  surface — the  pulmonary  pleura. 
The  narrow  space,  separating  the  two  pleural  leaves,  is  filled  with  a  viscid 
lubricating  fluid  which  establishes  cohesion  between  their  serous  surfaces, 
but  leaves  them  free  to  glide  over  one  another,  like  moist  panes  of  glass 
which  can  be  relatively  shifted,  but  not  forced  apart,  unless  air  is  made  to 


RANSOHOFF  MFMORIAL  VOLUME 


get  in  between  them.  Contact  between  the  two  surfaces  is  upheld  by  the 
air  pressure  within  the  lung  which  is  always  close  to  atmospheric  pressure/" 
Let  us  assume  now  that  an  incision  of  the  chest  wall  has  been  made  in 
ihe  course  of  an  operation,  opening  a  "virgin"  pleural  cavity,  viz.,  an  intact 
cavity  and  without  adhesions  between  lung  surface  and  chest  wall.  At  once 
air  is  admitted  between  the  two  pleural  leaves,  their  cohesion  is  destroyed, 
and  the  air  pressure  on  both  sides  of  the  visceral  (pulmonary)  pleura  of  the 
exposed  lung  is  equalized.  The  elastic  force  of  the  lung  tissue  is  thereby 
made  active;  the  lung  contracts  to  a  mass  of  the  size  of  a  fist  at  its  hylum — 
same  as  in  the  dog — and  the  opened  side  of  the  thorax  is  transformed  into 
a  cavity.  Immediately  the  respiratory  act  becomes  violently  disordered. 
The  excursions  of  the  thorax  leave  the  retracted  lung  unaffected,  because 
there  is  no  more  contact  between  it  and  the  chest  wall ;  its  lobes  have  lost 
their  function.  On  the  closed  side  of  the  thorax,  on  the  contrary,  the  co- 
hesion between  parietal  and  visceral  pleura,  and  therefore  the  function  of 
the  lung,  has  been  maintained.  However,  under  the  difference  of  air-pressure 
on  both  sides  of  the  mediastinum,  when  the  thorax  expands  during  inspira- 
tion, the  mediastinal  structures  plus  the  collapsed  lung  and  the  heart  with 
the  large  blood  vessels,  move  forward  and  partly  into  the  uninjured  side  of 
ihe  thorax,  the  lung  swinging  like  a  pendulum  suspended  on  the  trachea 
as  a  rod.  Inasmuch  as  the  mediastinal  contents  are  attached  by  means  of 
the  lower  portion  of  the  pericardium,  also,  to  the  diaphragm,  the  maximal 
lateral  displacement  occurs  at  about  the  center  of  the  mediastinum.  The 
whole  mass  moves  in  the  same  direction  as  the  chest  wall  of  the  uninjured 
side,  that  means  over  towards  the  side  of  the  lung  which  is  still  functioning, 
and  interferes  with  its  proper  distention.  The  functioning  lobes  are  thus, 
during  inspiration,  held  near  their  normal  expiratory  distention,  with  a  cor- 
respondingly reduced  change  of  air  in  them  and  reduced  oxygenation  of  the 
blood.  In  expiration  the  ]ienclulum  swings  the  other  way ;  the  whole  mass 
flops  back  into  the  open  cavitw  a  to-and-fro  rocking  of  the  heart  subject- 
ing the  large  blood  vessels  to  severe  bending  strains  in  alternating  directions. 
The  mediastinum  is  now  no  longer,  as  under  normal  condition,  the  evenly 
balanced  structure,  upon  which,  and  upon  the  rising  diaphragm  as  a  cushion, 
the  collapsing  chest  walls  squeeze  the  air  out  of  the  lung  through  the  nar- 
row glottis.  With  the  mediastinum  yielding  to  the  one-sided  pressure  upon 
it,  the  air  pressure  within  the  lobes  of  the  uninjured  side  only  gradually 
rises  high  enough  for  escape  of  the  tidal  air  by  way  of  the  glottis.  A  part 
of  this  tidal  air  rather  finds  an  outlet  into  the  incompressible  portion  of  the 

•The  intrapulmonarv  pressure  bcconips  slightly  reduced  (negative)  during  inspinitioii,  because 
the  distention  of  tli^  tlvrrix  r"Ti^  ^oni-wlinl  ahead  of  the  air  volume  a.lmittf.l  itivML-li  the  glottis. 
On  the  other  hand,  ih,  im  vu.mIih.ii  n  >  i,,,,sure  becomes  slightly  increa-.l  nn-nr,,  .  ,';,,inK  expira- 
tion, because  the     :.         i  ...t   allow   the  air  to  escape  iiuic  I  ■     the  thorax 

contracts.      A    si  ji. ■  f.iees    under    plivsiological    e^n'  '    iDkable.      It 

could  occur  only    «ii.     n.     ,,i    li.  ,,i    tln_.   King   to   drop  below  the   vain.       i    i  ,,    mi-nnal   elastic 

retractive  force  ol  liic  Iuuk  tl^■.uL■.  -;iy  ij  mm.  Hg.  This  latter  force  dineis  .il  vaiiuus  points  of 
the  lung.  It  depends  on  the  dtgiec  of  excursion  of  chest  wall  and  diapluagm  with  which  the 
particular  part  of  the  lung  is  in  contact.  At  the  apex  of  the  lung  and  along  the  spine  the  retrac- 
tive force  is  considered  to  be  practically  zero;  in  front  of  the  lower  lobe  it  is  ad  maximum,  varying 
.nt  other   points   between   these  extremes. 


WILLY  Ad  EVER 


bronchial  tree  of  the  lobes  of  the  collapsed  lung  where  it  has  but  atmos- 
pheric pressure  to  overcome,  and  not  the  additional  obstruction  represented 
by  the  glottis.  Thus  the  main  bronchus  of  the  collapsed  lung  with  its  first 
and  second  divisions — which,  as  just  stated,  have  retained  their  normal  size 
and  shape  on  account  of  the  cartilaginous  rings  within  their  walls,  same  as 
(he  trachea — becomes  a  "re-breathing  bag"  for  the  functioning  part  of  the 
lung.  In  this  way  the  collapsed  lung  appears  to  have  an  inspiration  during 
expiratory  movement  oi  the  thorax,  the  air  for  it,  however,  not  being  fur- 
nished from  without,  but  representing  a  part  of  the  expiratory  tidal  air  of 
the  functioning  lung;  that  means  air  which  should  have  left  the  respiratory 
system  by  way  of  the  glottis.  The  volume  of  the  tidal  air  is  thus  still  further 
reduced,  with  progressive  vitiation  of  the  shifted  air. 

At  the  same  time  a  persistent  chronic  "hyperemia"  invariably  develops 
within  the  collapsed  lung  on  the  injured  side.  Its  presence  there  was  proved 
by  most  interesting  experiments  conducted  by  Cloetta  of  Zurich,  Switzer- 
land. This  phenomenon  has  so  far,  it  seems,  not  received  the  attention  which 
it  deserves.  The  hyperemia  of  the  collapsed  lung  on  the  injured  side  nat- 
urally reduces  the  quantity  of  blood  in  the  general  system,  which,  as  stated 
before,  is  altered  in  its  quality  by  insufiicient  aeration. 

The  described  interference  with  the  normal  exchange  of  gases  in  both 
sides  of  the  lung  causes  a  gradual  accumulation  of  carbon  dioxide  in  the 
.system.  This,  in  turn,  produces  a  steadily  increasing  irritation  of  the  cen- 
ters of  respiration  and  circulation  by  way  of  the  pneumogastrics.  In  most 
instances  this  "vicious  circle"  soon  becomes  established  after  incision  of  the 
thorax.  Respiration  becomes  slower  and  deeper,  the  number  of  heart-beats 
is  reduced,  while  the  systolic  volume  of  blood  is  increased.  Dyspnea  in  its 
most  characteristic  picture  develops  and  persists. 

Such,  in  the  human  being,  is  the  general  course  of  the  dreaded  "acute 
pneumothorax."  As  stated  above,  it  occurs  only  in  a  certain  percentage 
of  the  patients,  coming  to  operation.  But  who  is  able  to  tell  beforehand 
"which"  patient  will  be  subject  to  its  deleterious,  or  even   fatal,  sequelae? 

The  symptoms  of  acute  pneumothorax  can  not  and  do  not  develop,  if 
we  prevent  the  collapse  of  the  lung;  that  is  to  say,  if  we  keep  the  lung  on 
the  open  side  of  the  thorax  in  distention  and  thereby  steady  the  mediastinum. 
This  can  be  done  by  the  employment  of  apparatus  embodying  the  "differential 
air-pressure"  method. 

Following  upon  scattered  ingenious  attempts  at  preventing  the  lung  col- 
lapse with  the  help  of  apparatus,  by  French  surgeons  (Quenu,  1895,  Tuffier, 
1896),  and  American  surgeons  (Fell,  1888,  Matas,  1898),  it  was  Ferdinand 
Sauerbruch  who,  in  1904,  by  his  experiments,  his  scientific  investigations 
and  his  constructive  genius,  placed  thoracic  surgery  on  a  safe  basis.  By  the 
publication  of  his  differential  Pressure  Method"  and  by  his  apparatus  he 
gave  to  the  surgical  world  the  means  for  operating  on  all  the  organs  situated 
within  the   thorax,   under  absence   of   disturbing  physical   conditions.     He 


RANSOHOFF  MEMORIAL  VOLUME 


made  it  possible  for  the  surgeon  to  operate  within  the  thorax  with  the  same 
tranquillity  of  mind  and  the  same  precision  as  in  other  cavities  and  parts  of 
the  body.  The  thoracic  cavity  thereby  was  opened  safely  to  the  surgeon, 
safely  in  the  real  sense  of  the  word.  viz..  without  forcing  the  operator  into 
taking  chances  with  his  patient's  life. 

He  also  showed  that,  in  case  of  injury  to  the  intra-abdominal  parenchyma- 
tous organs  in  the  vault  of  the  diaphragm  (liver  and  spleen),  work  upon 
them  could  be  safely  done  by  the  thoracic  route  (trans-thoracic  laparotomy). 

The  differential  pressure  method  aims  at  substituting  the  eiifect  of  ap- 
paratus for  the  normal  forces  sustaining  the  lung,  which  were  cut  out  by  the 
opening  of  the  thorax.  The  apparatus  has  to  supply  a  force  which  is  equal 
to  the  elastic  contraction  of  the  lung  tissue.    The  power  used  is  air-pressure. 

A  difference  in  air  pressure  can  be  obtained : 

1.  By  rarefying  the  air  over  the  outer  surface  of  the  exposed  part  of 
the  lung;  that  is  to  say,  by  producing  there  a  pressure  which  is  inferior  to 
the  atmospheric  pressure  within  the  bronchial  tree  and  alveoli — negative 
(differential)  pressure. 

2.  By  increasing  above  atmospheric  pressure  the  air-pressure  within  tiie 
entire  lung — positive  (differential)  pressure. 

\Mthout  exception  all  the  various  schemes  devised  for  the  neutralizing 
of  the  injurious  effects  of  the  acute  pneumothorax  are  based  on  that  alterna- 
tive, first  pronounced  in  so  many  words  by  Quenje  of  Paris. 

Making  use  of  either  one  or  the  other  of  these  methods  in  patients  suf- 
fering from  dyspnea  in  consequence  of  an  acute  pneumothorax,  one  will  see 
the  latter  disappear  and  respiration  become  normal  again.  One  will  also  see 
that  the  lung  on  the  opened  side  normally  participates  in  the  act  of  respira- 
tion. It  is  further  a  fact  that  differential  air-pressure  interferes  neither  with 
the  normal  respiration  nor  with  the  normal  circulation  of  the  blood.* 

The  tangible,  practicable  result  of  Sauerbruch's  labors  was  the  negative 
chamber.  Its  construct ioi^.  and  working,  its  advantages  and  defects  are 
known  to  my  hearers. 

An  amplified  type  of  negative  chamber,  constructed  on  the  basis  of  Sauer- 
bruch's principles,  I  had  built  in  New  York  in  1908,  and  I  experimented 
with  it  until  1910.  It  was  then  remodeled  and  became  part  of  the  apparatus 
of  the  Thoracic  Pavilion  of  the  Lenox  Hill  Hospital  of  New  York  City.  It 
permits  of  working  under  negative  as  well  as  under  positive  pressure  in  the 
course  of  one  and  the  same  operation.  The  change  from  one  pressure  to  the 
other  can  be  effected  instantaneously  and  without  the  necessity  of  reversing 
the  position  of  the  patient,  assistants,  instruments,  ec,  as  would  be  required 
in  Sauerbruch's  chamber,  were  the  pressure  to  be  changed  from  negative  to 
l)0.sitive. 


*.\  flight  incTPasp  in  pressure  lias  been  found  in  the  pu'innnary  artery  witli  some  stasis  in  I 
pnlmonary  vein,  also  some  decrease  in  arterial  blood  pressure,  when  usinK  positive  pressure.  Tto 
ever,  the  alterations  are  of  no  importance  so  lone  as  the  differential  pressure  is  not  pushed,  a 
this  is  never  indicated.  One  can,  therefore,  claim  that  new  risks  are  not  incurred  by  the  paiie 
who  submits  to  the  application  of  differential  air  pressure  during  operation. 

Page  m 


WILLY  MEYER 


The  rectangular  negative  chamber  at  the  Lenox  Hill  Hospital  is  so  far 
the  only  one  produced  in  America.  Originalh'  built  as  a  portable  apparatus. 
and  being  a  first  attempt,  it  is  naturally  open  to  improvement  in  one  or  the 
other  respect.  A  round  design  has  on  occasion  been  discussed,  constructed 
so,  that  the  chamber,  like  other  operating  rooms,  can  be  washed  out  with 
a  hose  stream;  also  additions  on  basis  qf  the  Swedish  chamber,  in  which  the 
mask  is  used  in  combination  with  negative  pressure,  an  improvement,  which 
requires  no  modification  of.  but  only  a  removable  attachment  to  our  present 
arrangements,  and  would  insure  undisturbed  asepsis  also  in  operations  on 
the  neck  in  the  course  of  esophageal  resections. 

The  negative  chamber  is  an  enlarged  pleural  cavity.  It  takes  care  with 
the  same  certainty  and  reliability  of  a  bilateral  as  of  an  unilateral  pneumo- 
thorax. It  represents  the  most  physiological  apparatus  in  existence  for  com- 
plicated intrathoracic  work  on  weak  and  reduced  patients.  It  permits  of 
the  use  of  differential  pressure  under  general  or  regional  and  local  anes- 
thesia. It  is  a  splendid  physical  apparatus,  which  will  always  retain  its 
scientific  as  well  as  its  practical  value. 

But  the  negative  chamber  is  expensive  and  stationary.  Surgeon,  assist- 
ants, nurses  and  patient  have  to  go  to  the  apparatus ;  the  apparatus  can  not 
be  brought  to  the  patient.  The  same  holds  good  for  a  number  of  positive 
(plus)  pressure  cabinets,  in  which  the  patient's  head,  that  is  to  say,  his 
bronchial  tree,  together  with  the  anesthetist — entire  or  in  part — are  placed 
under  increased  pressure. 

Sauerbruch's  work  made  a  great  sensatioii  in  the  surgical  world  and  met 
with  wide  recognition.  It  also  started  many  minds  devising  means  by  which 
the  same  ends  might  be  obtained  with  less  expense.  In  quick  succession 
followed  the  mask  method  Brat-Schmieden,  Tiegel,  Robinson  (1908-1910), 
Meltzer-Auer's  Intratracheal  In.sufflation  (1910),  and  Connell's  pharyngeal 
insufflation  (1912),  adapted  to  thoracic  surgery  by  Branower  (1913). 

Tiegel  worked  out  his  apparatus  on  the  basis  of  the  experimental  finding 
that  lack  of  oxygen  is  the  final  cause  of  death  in  acute  pneumothorax.  He 
proved  that  1  mm.  pressure  from  a  tank  filled  with  pure  oxygen  suffices 
to  avoid  trouble.  His  splendid  practical  apparatus  is  extensively  used  in 
European  clinics,  and  should,  particularly  for  use  in  emergencies,  form  an 
integral  part  of  the  equipment  of  every  operating  room  in  our  country,  too. 
Tiegel's  apparatus  can  be  quickly  wheeled  to  the  patients'  bedside,  a  feature 
of  great  value  in  case  of  trouble  in  the  after-treatment  of  thoracic  operations. 

Meltzer-Auer's  intratracheal  insufflation  represents  the  simplest  and 
most  nearly  perfect  of  all  positive  differential  pressure  methods.  Every  one 
of  you  knows  of  its  well-deserved  triumphant  march  all  over  the  world, 
within  the  last  eight  years.  In  two  directions  the  method  calls  for  attention 
and  skill — first,  that  introduction  of  the  tube  into  the  patient's  trachea  re- 
quires profound  general  anesthesia;  and   second,  that   a  person   is  needed 


Page  !,!» 


RANSOHOFF  MEMORIAL  VOLUME 


who  lias  been  trained  tu  make  the  introduction  of  the  tube  into  the  trachea 
properly  and  gently,  without  doing  harm  to  the  patient. 

Intrapharyngeal  insufflation,  which  was  originally  introduced  by  Karl 
Connell  of  the  Roosevelt  Hospital.  New  York,  as  a  method  of  anesthesia, 
and  later  on  adopted  to  thoracic  surgery  by  \N'.  Branower  of  New  York, 
with  the  help  of  an  ingenious  portable  apparatus,  promises  to  become  of 
greatest  value  for  thoracic  operations.  By  insufflating  pure  air.  or  air  mixed 
with  oxygen,  into  the  pharynx,  a  sort  of  air-storage  is  formed  in  that  local- 
ity, in  sufficient  volume  and  under  sufficient  pressure  to  prevent  the  flopping 
of  the  mediastinum  in  unilateral  pneumothorax  and  to  maintain  proper  oxy- 
genation of  the  blood. 

In  a  rough  wav.  foot-bellows  and  a  plain  rubber  tube,  introduced  into  the 
pharynx  through  tlie  nostrils,  can  substitute  the  apparatus  in  case  of  emer- 
gency. 

Thus,  we  now  have  at  our  disposal  four  useful  methods  for  maintaining 
differential  air  pressure,  from  which  we  can  select  according  to  inclination, 
opportunity,  and  the  needs  of  the  case  in  hand,  four  useful,  practical  dif- 
ferential pressure  methods,  which  enable  us  to  avoid  the  occurrance  of  acute 
pneumothorax.  Many  of  us  use  such  apparatus  in  our  thoracic  operations 
to  good  advantage  and  feel  that  we  do  not  want  to  be  without  them. 

On  the  other  hand,  there  are  a  number  of  colleagues  of  high  standing 
who  are  unwilling  to  accejit  dift'erential  air  pressure  as  an  underlying  prin- 
ciple in  thoracic  surgery,  and  claim  that  they  are  able  to  get  along  nicely 
without  its  use. 

Opposition  certainly  is  wholesome  and  to  be  welcomed.  It  is  necessary 
for  the  progress  of  science.  But  it  must  be  opposition  in  the  right  direction. 
Of  course,  we  all  have  to  individualize.  Why  should  not  a  surgeon,  if  he 
considers  it  advisable  in  a  given  case,  do  a  thoracic  operation  without  em- 
ploying differential  pressure  apparatus?  I  myself  have  done  it  in  many 
cases.  However,  what  I  claim  to  be  necessary,  and  always  have  had  in  my 
own  cases,  is  some  kind  of  differential  pressure  apparatus  close  at  hand, 
ready  for  instant  use,  should  the  necessity  for  its  use  arise  in  the  course  of 
the  operation  and  the  patient's  welfare  demand  it.  To  my  mind  the  time 
has  passed  when  any  surgeon  is  justified  in  saying  '"dift'erential  pressure  in 
thoracic  surgery  is  superfluous."  To  my  mind  it  is  wrong  to  promulgate 
such  views. 

For  the  sake  of  the  proper  evolution  of  thoracic  surgery  it  is  equally 
wrong,  I  believe,  to  want  to  give  to  the  surgery  of  the  lung  a  special,  an  ex- 
ceptional place  in  thoracic  surgery,  as  some  authors  have  lately  been  in- 
clined to  advocate.  We  should  not  separate  the  surgery  of  the  lung  from 
that  of  the  esophagus  or  any  other  intrathoracic  organ,  but  should  consider 
the  whole  field  within  the  thorax  an  entity  and  look  at  it  from  a  broad  and 
scientific  standpoint.  We  should  not  separate  thoracic  surgery  into  dift'erent 
categories.  We  speak  only  of  "abdominal  surgery."  and  there  is  only  one 
"thoracic  surgery." 

Page  iOB 


WILLY  MEYER 


In  this  connection  I  must  briefly  refer  to  the  teachings  that  have  of  lale 
emanated  from  a  number  of  great  Euro])ean  surgeons,  who  worked  at  the 
front  during  the  last  four  years  and  recently  traveled  through  our  country 
lecturing  on  their  experiences.  Under  the  correct  impression  that  air  pres- 
sure difference  was  necessary  for  safe  operating  within  the  thorax,  and 
having  no  apparatus  at  hand,  they  at  first  abstained  in  the  war  hospitals 
from  active  interference  in  chest  wounds.  Conservatism  was  their  watch- 
word in  these  war  injuries.  But,  compelled  by  many  unsatisfactory  results, 
they  finally  dared  go  ahead  without  using  differential  pressure,  and  saw  ex- 
cellent results  in  many  instances.  With  the  object  in  view  of  removing  all 
kinds  of  foreign  bodies  in  the  lung  or  pleural  sac,  they  made  an  intercostal 
incision,  cleaned  the  pleura,  pulled  out  the  lobe  of  the  lung  in  which  often 
the  X-ray  had  previously  located  the  seat  of  the  foreign  body,  incised  the 
lung,  extracted  the  missile,  stitched  up  the  pulmonary  wound,  dropped  the 
organ  back,  and  closed  the  chest  wall  air-tight  by  suture.  Many  of  these  pa- 
tients recovered. 

But  is  it  correct,  on  the  basis  of  such  satisfactory  experiences  in  war 
surgery  in  a  traumatized  and  often  inflamed  and  infiltrated  lung,  and  in- 
flamed or  infiltrated  mediastinal  structures,  to  assert  that  the  acute  pneumo- 
thorax is  something  quite  negligible,  something  not  worth  taking  into  con- 
sideration? Is  it  correct,  on  the  basis  of  experiences  gained  under  unusual 
conditions,  to  brush  aside  the  well-matured  conviction  of  a  century  that  the 
acute  pneumothorax  rather  is  a  matter  not  to  be  trifled  with,  to  ignore  the 
decades  of  endeavor  to  find  means  of  overcoming  its  recognized  dangers, 
and  to  draw  the  conclusion  that  dift'erential  pressure  is  a  ballast  in  thoracic 
surgery?  I  personally  think  that  it  would  be  an  error  to  accept  such  a  con- 
clusion. To  my  mind  the  operator  of  today  has  in  times  of  peace  no  right 
to  jeopardize  and  take  chances  with  the  patient's  life,  when  science  offers 
him  the  means  of  avoiding  them.  Would  the  surgeon  of  today  dare  omit 
any  of  the  details  of  aseptic  surgery,  because  the  ingenious  Spencer  Wells, 
before  the  antiseptic  and  aseptic  area,  successfully  performed  a  number  of 
ovariotomies  by  simply  washing  his  hands  carefully  in  plain  water  before 
the  operation?  If  a  modern  surgeon  were  to  do  his  and  lose  one  of  his  pa- 
tients he  would  be  condemned,  and  justly  so. 

Let  us  try  for  a  moment  to  analyze  the  experience  our  colleagues  have 
had  at  the  front.  For  the  sake  of  science  it  appears  necessary  to  do  so,  to 
try  to  explain  the  seeming  discrepancy  between  their  experience  and  that 
had  by  surgeons  when  operating  on  the  thorax  at  our  public  hospitals  in  times 
of  peace.  How  can  we  explain  the  absence  of  worrying  symptoms  in  many 
of  the  thoracotomies,  when  even  five  to  six  hours  after  the  wound  had  been 
inflicted,  the  chest  was  opened  freely  by  incision  without  the  use  of  dif- 
ferential pressure  apparatus? 

The  fact  has  been  established  in  the  course  of  the  war  that  over  50  per 
cent,  of  the  men  with  chest  wounds  died  on  the  battlefield.  The  surviving 
cases  reached  the  ambulance  or  field  hospital.     In  them  the  heart — usually 

Page  Ifi'J 


RANSOHOFF  MEMORIAL  VOLUME 


young,  strong,  and  not  diseased — had  withstood  the  acute  pneumothorax  and 
hemothorax,  and  the  lung  of  the  unopened  side  also  had  adapted  itself  to 
the  changed  conditions.  If  operated  upon  by  means  of  an  exploratory  in- 
cision and  without  pressure  apparatus,  often  the  at  first  serious  and  threaten- 
ing symiMoms  improved.  Why?  Simply  because,  as  we  all  know,  the  wide 
open  pneumothorax,  the  free  access  and  exit  of  air.  is  better  borne  than  tlie 
pneumothorax  coming  from  a  small  penetrating  wound,  through  wliich  air 
has  entrance,  but  very  frequently  an  obstructed  exit.  After  free  incision 
air  alone  reiilaces  the  blood  and  air  that  formerly  filled  the  pleural  cavity. 
The  mediastinal  tissues  are  apt  to  be  infiltrated  with  blood,  so  that  there  is 
little  flopping.  Besides,  the  surgeon  pulls  the  lung  out  of  the  thorax  and 
treats  it  as  the  case  may  require.  The  pulling  out  of  the  lung  into  the  wound 
opening  ( "Mueller's  trick")  steadies  the  mediastinum  still  further.  The 
lung  is  then  attended  to,  the  pleura  cleansed,  and  the  thorax  closed  hermeti- 
cally by  sutures ;  a  temporary  artificial  pneumothorax  is  left  behind.  The 
latter,  as  shown  by  Bastianelli's  splendid  investigations  on  the  Italian  front, 
favors  the  healing  of  the  injured  lung  and  its  gradual  expansion  with  ad- 
vancing absorption  of  air. 

The  results  obtained  by  our  colleagues  in  military  service  by  means  of 
aggressive  surgery  in  wounds  of  the  lung  have  certainly  been  brilliant  and 
deserve  the  highest  praise.  But  to  draw  any  sweeping  conclusions  from 
iheir  experience  zvith  reference  to  the  question  of  ivliether  or  not  the  em(<loy- 
iiient  of  differential  air  pressure  in  thoracic  surgery  in  general  is  a  necessity 
would,  to  my  mind,  be  a  serious  mistake.  How  many  of  the  wounded,  who 
died  after  thoracic  operations,  might  have  recovered,  could  some  differential 
pressure  method  have  been  employed  during  the  surgeon's  work,  can,  of 
course,  not  be  estimated. 

The  simplicity  of  the  above-described  o])erative  procedure  in  war  in- 
juries of  the  thorax  may  perhaps  have  impressed  particularly  those  who 
never  before  had  intentionally  entered  the  thorax  in  civil  practice,  and  who 
now  under  war  conditions  were,  by  sheer  necessity,  driven  to  thoracic  opera- 
tions. Under  the  stress  and  .strain  of  their  work  and  their  often  unexpected 
brilliant  results  of  radical  interference,  it  can  be  understood  that  many  were 
carried  away  by  their  enthusiasm,  that  they  generalized  and  gained  the  im- 
pression that  employment  of  differential  air  pressure  in  thoracic  surgery  is 
superfluous.  But  they  forgot  that  traumatic  chest  surgery  is  only  one  small 
chapter  of  thoracic  surgery. 

This,  "whether  or  not"  to  use  differential  air  pressure  in  thoracic  opera- 
tions is,  it  seems  to  me,  the  most  vital  question  of  the  hour  for  the  further 
safe  and  rapid  evolution  of  thoracic  surgery. 

The  idea  that  differential  pressure  apparatus  are  superfluous,  at  least  in 
lung  surgery,  has  naturally  also  got  into  the  medical  press,  and  thereby  been 
widely  disseminated.  What  wonder  that  our  colleagues  are  bewildered  and 
do  not  know  which  opinion  to  accept !  But  a  few  weeks  ago  I  met  a  col- 
league at  the  Academy  of  Medicine  in  New  \'ork.  wlio  works  at  a  hospital 

Page  I,t0 


IVILLY  MEYER 


with  plenty  of  accidental  chest  injuries.  We  got  into  a  discussion  on  thoracic 
surgery  and  differential  air  pressure.  He  said:  "Doctor,  nobody  knows  at 
the  present  moment  where  he  stands.  If  you  and  your  friends  of  the  Amer- 
ican Association  for  Thoracic  Surgery  want  to  do  the  profession  a  favor, 
throw  some  light  on  this  vital  question  and  state  whether  you  think  the  hos- 
pitals ought  to  provide  means  for  operating  within  the  thorax  or  not." 

Most  earnestly  would  I  invite  the  colleagues  who  believe  that  thoracic 
surgery  in  general  can  well  get  along  without  provision  for  the  maintenance 
of  the  physiologic  difference  in  air  pressure  existing  in  the  chest,  to  come 
into  the  arena  for  an  open  discussion  of  this  vital  question  which  has  been 
agitating  many  minds  for  the  last  twenty-five  years,  particularly  for  the  last 
fifteen  years,  and  submit  their  experiences  and  case  histories.  Let  us  discuss 
this  vital  question  fully,  but  let  us  settle  it,  at  least  among  ourselves. 

On  the  basis  of  practical  experiences  in  this  one  chapter  of  traumatic 
chest  surgery,  gathered  during  the  war,  modern  thoracic  surgery  in  general 
— I  beg  to  emphasize  this  once  more — can  not  afford  to  throw  overboard 
what  it  has  slowly  built  up  within  the  last  fifteen  years,  modern  thoracic 
surgery  in  general  can  not  afford  to  loosen  the  safe  foundation  on  which  it 
rests,  namely,  the  recognition  of  the  absolutely  vital  necessity  of  having 
ready  for  use  a  differential  air  pressure  apparatus  whenever  a  free  pleural 
cavity  is  invaded,  whenever  a  "virgin"  non-adherent  pleura  has  to  be  tra- 
versed in  order  to  reach  aft'ected  organs  lying  beyond  it  within  the  thoracic 
cavity. 

In  the  early  part  of  November  of  last  year  I  had  the  privilege  of  discuss- 
ing all  these  important  questions  with  the  five  members  of  the  commission 
that  had  come  over  from  England,  France  and  Italy  to  attend  the  American 
Congress  of  Surgeons.  All  five  came  to  the  'I'horacic  Pavilion  of  the  Leno.x 
Hill  Hospital.  They  examined  the  differential  pressure  apparatus  there  on 
hand:  the  negative  chamber  and  the  positive  cabinet,  Tiegel's  mask  ap- 
paratus, and  the  apparatus  for  insufffation.  After  a  prolonged  talk,  three 
of  the  five  took  my  point  of  view  and  conceded  the  necessity  of  doing 
thoracic  operations  with  proper  preparedness  for  dift'erential  pressure,  nega- 
tive or  positive. 

And  let  it  be  remembered  that  mask  method  and  insufflation  method,  in- 
tratracheal as  well  as  intrapharyngeal,  all  work  on  the  principle  of  positive 
(plus)  pressure  within  the  bronchial  tree;  that  is,  on  the  principle  of  dif- 
ferential air  pressure. 

Gentlemen,  I  would  ask  you,  not  to  consider  the  foregoing  remarks  a 
reflection  upon  what  other  colleagues  have  said  and  done,  but  to  take  them 
for  an  honest  attempt,  based  on  personal  experience  and  conviction,  to  assist 
in  finding  the  truth,  and  to  help  in  accelerating  the  evolution  of  thoracic 
surgery  for  the  benefit  of  suffering  mankind. 

After  all,  the  safeguarding  of  the  life  of  the  jiatient  entrusted  to  liis  care- 
is  the  first  duty  of  the  surgeon. 


BLOOD  FORMATION  IN  THE  LI\"ER  AND  SPLEEN  IN  EXPERI- 
MENTAL an.i^:mia.' 

Roger  S.  Morris,  M.  D. 
Cincinnati. 

(Fr.im  the  Lahnratnry  of  the  Second   Mc.lical   Clinic  in    Munich.^  Professor   Kr.   Mnller.   Director.) 

It  is  a  well-established  fact  that  the  chief  function  of  the  bone  marrow 
in  adult  life  is  haematopoiesis.  In  embryonic  life  the  liver  and  spleen  are 
haematopoietic  organs,  but  in  extrauterine  life  the  marrow  unaided  seems 
to  be  adequate  for  the  formation  of  the  blood  and  this  function  is  then  lost 
by  the  liver  and  spleen,  which  dilYer  in  a  corresponding  way  histologically 
at  these  two  stages  of  life.  Shortly  after  birth  there  is  apparently  less  need 
for  rapid  production  of  blood  corpuscles  than  in  the  embryo,  and  this  re- 
sults, therefore,  in  the  absence  of  recognizable  haematopoietic  (myeloid) 
tissues  in  liver  and  spleen,  while  at  the  same  time  evidence  of  extensive  pro- 
liferation is  less  marked  in  the  bone  marrow.  If,  however,  unusual  de- 
mands are  made  upon  the  bone  marrow  for  one  reason  or  another,  as,  for 
example,  through  the  loss  of  a  large  quantity  of  blood  from  hasmorhage, 
signs  of  increased  activity  are  found;  and  in  certain  instances,  as  in  most 
cases  of  pernicious  anaemia,  the  alteration  of  the  marrow  may  be  such  that 
it  resembles  in  a  remarkable  manner  that  seen  in  the  embryo — a  reversion 
of  the  marrow  to  the  embryonic  type,  as  Ehrlich  pointed  out  many  years 
ago.  Here,  to  all  intents  and  jjurposes,  the  problem  of  the  pathological 
physiology  of  blood  formation  in  severe  anaemias  has  remained  until  the 
recent  publications  by  Meyer  and  Heineke  (1.  2)  of  the  results  of  their 
"Studies,  which  prove,  they  believe,  a  similar  reversion  to  the  embryonic 
type  on  the  part  of  the  liver  and  spleen  in  cases  of  grave  anaemia. 

In  a  careful  examination,  both  clinical  and  histological,  of  eleven  cases 
of  severe  anaemia  (1)  which  came  to  autopsy  (seven  cases  of  pernicious 
anaemia,  two  of  anaemia  following  sepsis,  one  of  anaemia  associated  with 
cardiac  disease,  and  one  of  so-called  leukanaemia)  and,  in  their  second  more 
complete  study  (2),  of  an  additional  two  cases  of  pernicious  anaemia  diag- 
nosed at  autopsy,  Meyer  and  Heineke  have  found  strong  evidence  of  blood 
formation  in  the  liver  and  spleen.  The  organs  were  studied  from  smears 
made  from  the  freshly  cut  surfaces  post-mortem  and  from  histological  sec- 
tions. In  the  spleen  they  found  alterations  in  all  instances ;  these  consisted 
in  decrease  in  size  of  the  follicles  and  collections  of  mononuclear  cells,  vary- 
ing greatly  in  size  and  in  the  relation  of  nucleus  to  cell  body,  within  the 
venous  sinuses — the  so-called  Billroth's  veins  of  the  spleen.  These  cells 
they  identified  from  a  study  of  the  smears  and  sections,  as  normoblasts,  mye- 
locytes, and  mononuclear,  non-granular,  "lymphocyte-like"  cells.  Changes 
in  the  liver  were  not  so  constantly  present,  but  were  found  in  seven  cases. 

[From  the  Johns  Hopkins  Hospital   Bulletin,   June-July,    1907.] 

'  Presented  before  the  .American  .\ssociation  of  Pathologists  and  liaclcriolosists  at  WashinRton. 
n.  C.  .May  7,   1907. 

'  These  experiments,  begun  in  Prof.  Muller's  laboratory,  have  lieen  continued  in  the  lalinratorv 
of  the  medical  clinic  of  Prof.  Dock  of  the  fniversity  of  Michijjan  and  in  that  nf  Prof.  Barker  of 
The  Johns  Hopkins  University. 


ROGER  S.  MORRIS 


They  were  of  two  kinds  :  (a  )  In  three  instances  they  found  groups  of  mono- 
nuclear cells  collected  in  the  liver  capillaries,  chiefly  in  the  peripheral  portion 
of  the  lobules,  consisting  of  lymphocyte-like  cells,  normoblasts,  and  mye- 
locytes, and  (b)  in  four  cases  there  were  collections  of  large  mononuclear 
cells  rich  in  proto])lasm  in  the  periportal  connective  tissue,  usually  arranged 
about  the  cells,  with  many  mononuclear  eosinophile  cells  also.  In  the  smears 
made  from  both  spleen  and  liver  the  proportion  of  nucleated  red  blood  cells 
and  myelocytes  greatly  exceeded  that  found  in  preparations  made  from  the 
blood.  The  liver  sections  corresponded  very  closely  in  appearance  with 
those  of  the  human  embryo's  liver  at  about  the  seventh  month,  while  the 
spleen  was  also  embryonic  in  type.  No  collections  of  cells  like  those  described 
in  the  liver  and  spleen  were  found  in  any  other  organs,  and  the  authors  felt 
justified  in  the  belief  that  the  changes  represented  true  blood  formation 
rather  than  a  wandering  in  of  cells  from  the  circulation,  the  cell-nests  re- 
sembling closely  those  seen  in  the  bone  marrow. 

With  the  view  of  determining  whether  similar  changes  could  be  repro- 
duced in  animals  by  the  administration  of  substances  known  to  cause  auiemia, 
experiments  were  begun  by  the  writer  at  the  suggestion  of  Prof.  Miiller  and 
Dr.  Meyer.  The  rabbit  was  the  animal  chosen  and  pyrodin  (acetylphenyl- 
hydrazin)  was  selected  as  the  toxic  agent.  The  attempt  was  made  to  pro- 
duce a  chronic  ansmia  of  rather  severe  grade,  so  that  the  bone  marrow 
would  be  overtaxed  in  blood  formation.  By  this  means  it  was  hoped  that 
the  liver  and  spleen  would  reassume  one  of  their  embryonic  functions  and 
assist  in  the  production  of  blood. 

The  animals  were  kept  in  well-cleaned  and  ventilated  cages  and  were 
fed  with  oats  and  greens  daily.  Frequent  examinations  of  the  blood  were 
made,  including  counts  of  both  red  and  white  cells,  estimation  of  hemo- 
globin, and  smears.  Pyroden  was  given  about  5:00  p.m.,  the  dose  depend- 
ing upon  the  blood  count  made  earlier  in  the  afternoon.  A  solution  of 
pyrodin  in  water  was  prepared  in  which  1  c.c.  equaled  0.005  gram  pyrodin. 

Experiiuent  A:  Rabbit  I.  Male.  Weight,  2,665  grams.  Pyrodin  ad- 
ministered bv  stomach  tube. 


Date 

R.  B,  C. 

w.  n.  c. 

I 

19()5 

30-VI 

.S.SSO.OOO 

12,000 

3-VII 

5,200,000 

7,080 

4-VII 

S-VII 

5,350,000 

9,600 

60% 

6- VI I 

4,090,000 

7-VII 

3,650,000 

14,732 

43% 

8- VI I 

2,875,000 

10- VI I 

2,105,000 

17,166 

25% 

11 -VII 

2,200,000 

12-VII 

2,155,000 

11,776 

17% 

13-VII 

1,830,000 

14-VII 

1,940.(0) 

13,954 

25% 

IS-VU 

2.375,<10I> 

11  ,,354 

1  S-VII 

2.375,(HX> 

11, .354 

31% 

17-Vll 

2,435,000 

3,820 

46% 

IXA'H 

3,4Q0,(KXi 

5,154 

46% 

19-\"I1 

3.!25,tXX) 

HI).  Pyrodin  Remarks 


0.015 

0.01 

(Sahli)     0.02 


0.02 

0.03 

0.02 

0.02     Xo  free  Hh.  in  serum. 

0.02 

0.02 

none  .Animal  weak.     \\t.  -  1,904  gnis 

none 


0.02 

0.03     Kresh 

0.035  Serum 


RANSOHOFF  MEMORIAL  VOLUME 


Date 

R.  B.C. 

W.  B.  C. 

HI,. 

Pyrodlii                   Remarks 

1905 

20-VIF 

2.633,l!(M_) 

8,660 

37%   (Sahli) 

0.03 

21-\-|I 

2.26.%(I0() 

0.03     Serum    fainlv   pink. 

J.'-\ll 

l.Qlo'dUi 

15.466 

26% 

i)M     .Misccss  ..f  left  ear. 

-M-\'ll 

I  !(>.'()  IHKI 

18,688 

25% 

2?-\ll 

1.93(l.(»!ll 

(Sr 

26-Vll 

1.9,?7,(HNt 

9,622 

34% 

0.03 

27-VII 

2.24,\<X)() 

0.04 

28-VII 

1,785,(K)() 

12.622 

31% 

0.03     Fresli    .solution    ,,f    pvrn.liii. 

29-vn 

0.02 

30- vn 

1,875,000 

11,266 

29% 

0.03 

31-vn 

1,230,000 

0.02 

i-viir 

1.450,000 

33,822 

23,% 

0.025  Ear  ahseess  evaeiiated. 

2-VnT 

1,925,000 

0.03 

3-\'llI 

1,565.(K)0 

8,600 

2i%          " 

t1.03 

4-VIII 

1,385,000 

Died. 

Death  occurred  some  time  between  11:45  a.m.  and  2:45  p.m.  At  au- 
topsy the  body  was  warm.  There  was  slight  rigor  mortis  in  the  legs. 
Weight  =  2,065  grams.  All  of  the  organs  were  very  dark  in  color.  The 
spleen  was  enlarged,  measuring  8  x  1.5  x  2  cm.  The  bone  marrow  was  dark 
reddisli  brown  in  both  femurs.  The  lungs  were  air-containing  throughout 
and  there  were  numerous  pin-head  hsemorhages  on  the  surfaces.  The  kid- 
neys sliowed  pigmentation  of  the  cortex ;  this  was  especially  marked  along 
llie  inner  edge.  Heart  muscle  was  paler  than  normal.  There  was  very  little 
lilood  in  the  organs.    No  fluid  in  peritoneum,  pleurae  or  pericardium. 

Microscopical  Examination. — The  tissues,  fixed  in  alcohol,  mercuric 
chloride  and  acetic  acid,  and  formaldehyde,  were  embedded  in  paraffin  and 
in  celloidin,  sectioned,  and  stained  with  hsematoxylin  and  eosin,  van  Gieson's 
stain,  and  borax  carmine  with  potassium  ferrocyanide  and  hydrochloric  acid. 

Bu)\c  Marroxv. — The  marrow  of  the  shaft  of  the  femur,  normally  fatty 
in  full-grown  rabbits,  showed  marked  hyperplasia,  the  fatty  marrow  being 
entirely  replaced  by  myeloid  tissue.  A  study  of  smears,  stained  with  lijeina- 
toxylin  and  eosin,  May-Griinwald's  stain,  and  Ehrlich's  triple  stain,  in  con- 
junction with  that  of  the  sections,  shows  that  the  non-granular  mononuclear 
cells  (myeloblasts)  are  greatly  in  the  majority.  There  are  many  normo- 
blasts and  many  intermediates,  but  no  typical  megaloblasts.  Myelocytes  are 
also  numerous.  There  are  a  few  phagocytes  and  many  megalokaryocytes 
(see  Fig.  1). 

S/'lecn. — There  is  marked  destruction  of  the  cells  of  the  pul]).  The  fol- 
licles are  diminished  in  size  and  in  some  instances  the  central  artery  is  almost 
completely  devoid  of  lymphoid  tissue.  In  the  vettoiis  sinuses  there  are  large 
7H'sts  of  mononuclear  cells  with  non-granular  protoplasm  and  rather  deeply 
staining  nuclei  (see  Fig.  2).  There  is  an  enormous  number  of  phagocytes  con- 
taining fragments  of  red  blood  cells  and  brown  amorphous  pigment,  both  in 
the  capillaries  and  venous  sinuses  and  in  the  pulp.  Megalokaryocytes  are  fairly 
numerous.  Smears  made  from  the  freshly  cut  surface  of  the  spleen  show 
maiiy  non-granular  mononuclead  cells  like  those  in  the  bone  marrow,  vary- 
ing in  size  from  that  of  a  red  blood  cell  to  a  cell  whose  diameter  is  twice  as 
large  or  greater,  the  protoplasm  being  very  basophilic,  the  nucleus  a  little 
paler  (May-Griinwald  stain).     Many  of  the  nuclei  have  brick  red  blotches 

Pane  m 


ROGER  S.  MORRIS 


which  extend  at  times  into  the  protoplasm.  From  the  former  cell  one  sees 
apparently  all  gradations  to  the  typical  myelocyte,  i.  c,  from  cells  having 
few  pseudo-eosinophile  or  eosinophile  granules  to  those  having  many.  There 
is  a  moderately  large  number  of  myelocytes.  In  the  smears  there  are  also 
a  few  normoblasts.  Very  few  polymor])honuclear  pseudoeosinophiles  are 
seen  and  rarely  one  finds  a  mastcell.  There  are  many  pale,  free  nuclei. 
Phagocytes  are  present. 

Liver. — The  section  of  the  liver  presents  a  remarkable  picture.  The 
liver  cells  are  well  preserved,  but  show  considerable  pigmentation,  hemo- 
siderin being  present  in  large  amount.  The  liver  capillaries  are  much 
ci'ldened.  ami  in  tlicin.  especially  in  the  periphery  of  the  lobules  (see  Fig.  3), 
are  vests  of  mononuclear  cells  (Fig.  4),  having  non-granular  protoplasm 
and  deeply  staining  nuclei  (hasmatoxylin  and  eosin).  The  cells  of  the  intra- 
capillary  nests  resemble  large  lymphocytes,  though  at  times  apparent  erythro- 
blasts  (normoblasts)  and  undoubted  pseudoeosinophile  myelocytes  are  seen. 
Some  of  the  cells  show  mitotic  figures.  The  number  of  cells  seen  in  the 
central  veins  of  the  lobules  and  in  the  larger  vessels  of  the  liver  is  relatively 
much  less  than  that  in  the  capillaries  of  the  peripheral  part  of  the  lobules, 
while  in  the  central  zone  of  the  lobules  nucleated  cells  are  very  scarce  in  the 
capillaries.  Occasionally  a  megalokaryocyte  is  found,  often  in  connection 
with  a  collection  of  mononuclear  cells  (see  Fig.  5),  at  times  independent  of 
a  cell-nest.  In  the  capillaries  there  are  al.so  phagocytes  like  those  seen  in  the 
spleen.  No  collections  of  mononuclear  cells  are  found  in  Glisson's  capsule, 
though  there  is  a  myelocyte  occasionally.  Smears  made  from  the  liver  re- 
semble in  every  way  those  made  from  the  spleen. 

Kidneys. — These  organs  show  no  noteworthy  alteration  except  for 
marked  hsemosiderosis  of  the  cortex. 

Lungs. — There  is  moderate  congestion.  A  few  megalokaryocytic  emboli 
are  seen. 

The  remaining  organs  showed  nothing  of  importance. 

In  this  experiment  we  have,  then,  a  chronic  anaemia  produced  by  admin- 
istration of  pyrodin  in  which  a  maximal  etYort  has  been  made  on  the  part 
of  the  organism  to  regenerate  the  blood.  Not  only  is  the  bone  marrow 
hyperplastic,  but  the  liver  and  spleen  which  present  a  very  striking  resem- 
blance to  those  organs  in  the  rabbit's  embryo  during  the  stage  when  they 
are  actively  engaged  in  blood  formation,  may  be  assumed  to  aid  in  the  for- 
mation of  blood.  The  picture  parallels  that  described  by  Meyer  and  Heineke 
in  pernicious  anaemia  in  man  to  a  striking  degree  in  the  presence  of  myeloid 
tissue  in  both  liver  and  spleen,  and  further  resemblances  to  pernicious 
anaemia  are  found  in  the  high  color  index  which  existed  during  life,  the 
blood  crises,  the  presence  of  "nuclear  particles"  in  the  red  blood  cells  (to 
be  described  in  another  paper),  the  myeloblastic  type  of  bone  marrow,  the 
phagocytosis  in  the  haematopoietic  organs,  and  the  hreniosiderosis  of  liver, 
spleen,  and  kidneys. 


RANSOHOFF  MEMORIAL  VOLUME 


Experiment  B:   Rabbit  II.     Malt 
siibcutaneously  and  by  stomacli  tube. 


Weight.  1,285  grams.    Pyrodin  given 


Date 

R.  n.  c. 

VV.  B.  C. 

HI). 

Pymdii 

1                   Remarks 

190.^ 

l-\ll 

.^2(KUx;o 

9,(XH) 

,3-\lI 

Cm 

.    O.OI 

4-Vll 

,1055.(1011 

7,140 

4(»%     (Salili: 

1     0.(K)5 

5-\'ll 

0.(X)5 

6-VlI 

2.7(().0(Hl 

9,732 

il% 

(t.(Kt5 

7-\II 

2.900,(X)(t 

0.01 

8-vn 

2,675,(KI(I 

14,6(X1 

,35% 

0.01 

lO-VlI 

2,350,000 

0.01 

ll-VII 

2.655,0(K) 

16,110 

41% 

001 

HI),    estimation    verilicd. 

12-VlI 

2,265,1X10 

0.01 

13-VII 

2,465,0a» 

8.510 

35% 

0.015 

Wt.  =  1.335    Kms. 

14-VII 

2,lSO,rM»0 

10,688 

0.01 

15-VIl 

2,330,tKK) 

5.576 

37% 

O.OIS 

17-VII 

2,410,000 

11,600 

36% 

0.02 

18-VII 

2,610.000 

0025 

Fresh  solntion  of  pvrudin. 

19-vir 

2.585,000 

10,884 

38%          " 

0.03 

20-\II 

2,160,000 

i).02 

21-VIl 

2,060,0<K) 

2-::-:<^2 

^.I'Tc 

0.025 

22- VI 1 

1,725,(1(10 

0.02 

23- vn 

1,212,0««) 

33.488 

267c 

none 

24-VII 

1,8,^5,(HK1 

0.02 

25-VIT 

2,(>!5,0(K) 

10.510 

3S% 

0.03 

26-VII 

1.262,(VI0 

0.02 

27-VII 

950,(X«) 

16.510 

21% 

nnne 

28-VII 

1  775  (X)0 

0.025 

29-VII 

l,95O,0(XI 

26,310 

,34% 

0  03 

30-^'II 

1,85(>,()00 

0.03 

.M-VII 

1,720,()(X) 

19.8tX) 

22% 

0.03 

l-\-III 

1,480,0(X) 

0.035 

2-\'llI 

1 ,365.000 

21.044 

22%          " 

0.03 

3-\-ni 

1,500,0(X) 

0.03 

4-\'III 

1,375,(XX) 

25,954 

25% 

none 

5-VIH 

1,475,0(X) 

0.03 

Pyrodin  by  stoinaeli  UiUc. 

7-VIlI 

2,1(X).(HX) 

14,354 

.18% 

0.03 

Pyrodin  l)y  stoniaeh  tube. 

8-\'III 

2,230,(XX) 

0.04 

Pyrodin  bv  stomach  tube. 

Q-\-TT! 

2,125.000 

30,250 

25% 

0  04 

Fresh  solution  of  pvrodin. 

!0-\-ni 

1.415,000 

0.04 

Pyrodin  by  stomach  tube. 

Death  during  the  night.  Autop.sy  at  12:15  p.m.  There  was  a  small 
amount  of  clear,  light  yellow  fluid  in  the  peritoneum.  Right  lung  showed 
moderate  hypostasis  and  oedema.  Otherwise  the  organs  resembled  in  every 
particular  those  from  rabbit  I. 

]\Iicuoscopic.-\L  Ex.\MiN.-\Tiox. — The  tissues  from  this  rabbit,  as  well 
as  those  from  the  remaining  animals,  were  all  treated  as  in  rablait  I.  experi- 
ment A. 

Bone  Mamn^-. — This  resembles  in  all  respects  that  seen  in  rabbit  I.  In 
the  smears,  however,  there  are  a  few  nucleated  red  cells  which  may  be 
classed  as  megaloblasts. 

Spleen. — There  is  marked  necrosis  of  the  pulp  and  the  Malpighian  fol- 
licles are  reduced  in  size.  In  places  in  the  venous  sinuses  there  are  groups 
of  mononuclear,  non-granular  cells  like  those  in  experiment  .\.  In  one 
grou])  there  were  two  megalokaryocylcs  and  several  phagocytes,  and  in  one 
of  the  non-granular  cells  a  mitotic  figure  was  seen.  Haemosiderosis  is 
marked.      The   erythrocytes   ihroughout    the   si)ieen   are    for   the   most   part 


ROGER  S.  MORRIS 


slirunken  and  distorted.  Smears,  stained  as  in  experiment  A,  show  very 
many  cells  resembling  lym])hocytes  with  a  moderate  number  of  normoblasts 
and  myelocytes  which,  however,  seem  less  numerous  than  in  rabbit  I.  There 
are  many  phagocytes  and  jiractically  every  red  blood  cell  is  distorted. 

Liver. — There  is  marked  fatty  degeneration,  afifecting  chiefly  the  cells 
of  the  central  part  of  the  lobule.  There  is  no  dilatation  of  the  capillaries 
and  no  intracapillary  nests  of  cells  are  to  be  seen.  No  megalokaryocytes  are 
found.  There  is  considerable  hfemosiderosis.  Smears  show  a  few  polymor- 
phonuclear pseudoeosinophiles,  V^ery  rarely  one  finds  a  normoblast  or  a 
myelocyte ;  they  seem  to  be  about  as  numerous  as  they  are  in  the  heart's 
blood.  Mastzellen  are  comparatively  numerous.  A  few  phagocytes  are 
seen. 

Kidneys. — Marked  h;eniosiderosis  of  the  cortex;  otherwise  practically- 
negative. 

The  remaining  organs  are  negative. 

The  spleen,  which  has  been  active  in  this  experiment  as  a  li;ematopoietic 
organ,  has  assisted  the  bone  marrow  in  the  attem[)t  to  compensate  for  the 
anaemia,  but  there  is  no  evidence  of  hsmatopoiesis  in  the  liver. 

Experiment  C:  Rabbit  III.  Male.  Weight,  2,170  grams.  Pyrodin  given 
by  stomach  tube. 


Date 

R.  B.  C. 

W.  B. 

C            III). 

I'vnulin 

Kcniarks 

1906 

Il-IV 

S,()5(»,()00 

9,020 

53%    (Micschcr) 

nunc 

18-IV 

6,025,(:O0 

12,400 

62% 

(Mil 

19-1 V 

5.820,000 

0.02 

2.3-IV 

3,850,000 

12,500 

44% 

0.02     Raliliit 

sccnis   lifeless. 

23-IV 

3,487,000 

0025 

25-1 V 

3,275.000 

14,160 

34% 

0.04 

26-IV 

2,125,000 

none 

27-1 V 

1,843,000 

2S-1V 

1,093,000 

12,480 

■■3% 

30-1 V 

1,925,000 

7,00<_1 

39% 

■' 

1-V 

3,441,000 

8,600 

47% 

0.03 

2-V 

2,075,000 

10.640 

39%        ;; 

3-V 

3,721,000 

9.280 

'•       Difficult 

y  in   passing  tube. 

4-V 

3,833,000 

5.600 

51% 

■■       Difficult 

y  in   passing  tube. 

5-V 

4,087,000 

6.932 

58% 

(1.035 

7-V 

2,975,000 

12,532 

42% 

8-V 

2,750,000 

13,120 

Z?,% 

0.035 

9-V 

2,600,000 

15,600 

32% 

0035 

10-V 

2,450,000 

26,800 

25%        ;; 

0.04 

11-V 

1,500,000 

26.300 

none 

12-V 

1.400.000 

20,400 

19%        ;; 

0025 

14-V 

2,312.000 

5,849 

0.04 

15-V 

2,300,000 

6,620 

26% 

0.04     Fresh   s 

.olution    of    pvrocbi 

16-V 

1,993,000 

19,520 

23% 

004 

17-V 

1,858,000 

8.700 

15% 

none 

18-V 

1,730,000 

7.464 

16% 

I9-V 

1,935,000 

3,776 

21% 

0.04 

21-V 

2,566.000 

4,088 

28% 

0.045 

22-V 

2.020,000 

7,064 

20% 

none 

23-V 

2.012.0(X) 

17,600 

22% 

0.04 

24-V 

1,762,000 

5,552 

18% 

none 

25-V 

1,525,000 

8.9<^1 

17% 

26-V 

1,735.000 

7.464 

16% 

28-\' 

2,225,000 

vm 

28% 

0.045 

RANSOHOfl'  MEMORIAL  VOLUME 


DalL' 

K.  B.  C. 

\\.  B. 

C.            Hb.             Pyrudii; 

1906 

J9-\" 

Z360.000 

5,200 

19%  (Miesclier)     0.04S 

30-\- 

1.880,000 

16.800 

15%            ••             0.045 

31-V 

1,293,000 

21.500 

12% 

1-VI 

1,044,000 

18,932 

11% 

2-V\ 

1.. Ml. 000 

10.044 

m 

Death  occurred  l)et\vefn  If)  :00  and  1 1  :()()  a.  in.  un  June-  4.  UHY..  Autop.sy 
at  3  :00  p.  m. 

There  were  .small  yellowish  nodules  in  the  liver.  >onie  of  which  had  ex 
tended  to  the  surface  of  the  organ  ;  they  were  slightl\  elevated,  flat  across 
the  top,  and  rather  finn  in  consistency.  No  areas  of  softening  were  found 
in  them  on  section.  In  other  respects  the  organs  dift'ered.  niacroscopically. 
in  no  essentials  from  those  in  the  preceding  rabbits. 

Microscopic. \i.  E-K.v.min.vtion'. — Bone  Marrcn^'. — There  is  marked  hy- 
perplasia of  the  myeloid  tissue,  the  granular  marrow  cells  (myelocytes)  be- 
ing in  the  majority.  The  islands  or  cell-nests  described  by  P.unting  are  vveil 
seen  and  many  of  the  large  non-granular  cells  in  the  center  of  the  nests 
show  karyokinetic  figures.  Phagocytes  are  present.  Tn  the  smears  there 
are  many  free  pseudoeosinophilic  granules;  there  are  very  few  intact  myelo- 
cytes. 

Spleen. — This  resembles  the  spleen  in  rabbits  I  ;iud  II  in  the  decrease  in 
size  of  the  splenic  follicles,  the  diminished  number  of  cells  in  the  i^ulp,  and 
the  presence  of  a  few  megalokaryocytes.  Phagocytes  are  jjresent  in  enor- 
mous numbers.  A  few  pseudoeosinophile  myelocytes  are  found  in  the  pulp. 
In  the  venous  sinuses  and  rarely  in  a  capillary,  collections  of  mononuclear 
cells  resembling  large  lymphocytes  are  seen;  at  times  a  megalokaryocyte  is 
present  in  these  collections  of  mononuclear  cells.  Evidences  of  mitosis  are 
not  lacking  in  the  cells  collected  in  the  venous  sinuses.  Smears  show  large 
numbers  of  nucleated  reds,  as  many  as  six  being  found  in  one  held  (Leitz. 
1/12  oil  immersion;  ocular.  I\').  The  majority  of  the  nucleated  reds  are 
normoblasts,  though  there  are  many  intermediates  and  rarely  a  megalo- 
blast  ?).  No  definite  cell  division  figures  are  found  in  the  smears.  There 
is  a  great  number  of  lymphocyte-like  cells  resembling  the  non-granular, 
mononuclear  cells  of  the  bone  marrow.  .\  moderate  number  of  jiseudo- 
eosinophile  myelocytes  is  present.     Mastzellen  are  very  scarce. 

Liver. — The  liver  cells  show  little  change  other  than  ;i  moderate  pig- 
mentation of  the  cells  of  the  peripheral  zone  of  the  lolnilo.  In  the  liver 
capillaries,  both  in  the  central  and  peripheral  zones,  there  are  many  pseudo- 
eosinophile leucocytes,  mostly  polymorphonuclear  with  only  an  occasional 
mononuclear.  Megalokaryocytes  are  not  .seen.  Glisson's  capsule  is  un 
altered.  The  nodules  found  at  autopsy  present  a  central  necrotic  area  sur- 
rounded by  granulation  tissue.  Smears  show  many  polymorphonuclear 
pseudoeosinophiles.  very  few  norninblasts  and  mastzellen.  few  pseudoeosino- 
phile mvelocvles. 


ROGER  S.  MORRIS 


J'lic  remaining  organs  art  nt-gative  c.xct-pt  for  iiignK-nlation  of  tliu  renii 
tex. 

\\\-ighi.  2,.^0U -rani>.     I 'vrodin  si\  e- 


Ex 

periniciil  D 

:    Rabl. 

ii  l\  .     Male.     \\\-ighi. 

siibciit 

aneouslv. 

Dale 

K.I  i.e. 

W.  1!. 

C.           1 

11,                I'vr.Hln 

19t)6 

12-IV 

5,855,l->liO 

4.176 

55%    uMic'SclK-ri     none 

18-IV 

5,662,0a) 

59% 

0.01 

19-IV 

5,86O,0UO 

6.800 

59% 

0.015 

23-IV 

5,612,000 

51% 

0.015 

24-IV 

4,820,000 

5,200 

44% 

0.03 

25-1 V 

5,170,001 

0.04 

26-IV 

.\  125.000 

8,844 

43% 

0.03 

27-IV 

1,664,000 

none 

28-I\- 

1.406,000 

6,920 

11% 

.^o-i\- 

1.440,000 

2,800 

17% 

1-V 

l,941,Um) 

2.664 

26% 

2-\" 

.1360,000 

2.488 

39% 

0.03 

3-\" 

.1,1 64,000 

3,100 

45% 

0.035 

4-V 

2,714,000 

4,700 

43% 

0.03 

5-\" 

2,4(_)0,OUO 

6,400 

43% 

0.03 

7-\ 

2.100.000 

7,128 

35% 

0.03 

8-V 

2,125,000 

13,800 

25% 

•;             0.035 

q-v 

1.662.000 

18,080 

15% 

lO-V 

1.237.000 

4,932 

18% 

u 

ii-\" 

1.807,000 

5.376 

24% 

0.025 

ij-\' 

2.014.000 

3,864 

28% 

0.035 

14-V 

1,468,000 

4,480 

22% 

0.03 

]S-\ 

1,785.000 

4,852 

20% 

0.035 

16-\- 

1,262,000 

11.200 

15% 

none 

17-\ 

1.750,000 

4,932 

19% 

\SA- 

2.160.000 

2,640 

24% 

0.035 

19-V 

2.050.aX) 

.1100 

23% 

;;          0.035 

21 -V 

1,281.000 

3,360 

12% 

wi-ak.      l''nr   roiit;li. 

Animal  died  between  11:00  a.m.  and  1:00  p.m.  on  May  22.  1906.  Au- 
topsy at  5:00  ]i.  ni.  Large  red  clots  in  both  \entricles  and  extending  into 
the  aorta  :  |iracticaliy  no  fluid  l)!ood  in  any  of  the  vessels  or  organs.  The 
latter  are  macroscopically  the  .'-ame  as  in  rabbit  I.  As  in  the  |)receding  ani- 
mals, no  lymph  glands  or  hremolymph  glands  were  found, 

MxCROSCOPTCAL  EXAMINATION". — Boiic  Mciirow. — The  section  shows 
marked  hyperplasia  of  the  bone  marrow  of  the  myeloblastic  type.  In  tin 
smears  the  myeloblasts  are  by  far  the  most  numerous,  the  erythroblasts  and 
granular  marrow  cells  being  relatively  few  in  number. 

Spleen. — The  alterations  in  the  s[)Ieen  resemble  those  seen  in  the  three 
previous  experiments,  but  they  are  less  marked.  Megalokaryocytes  are 
present.  Smears  show,  in  addition  to  many  lymphocyte-like  cells,  a  few 
normoblasts  and  myelocytes. 

Liver. — Sections  show  very  little  alteration.  In  the  smear  only  two  nor- 
moblasts were  found  after  prolonged  search,  not  more  than  smears  from  ili.- 
blood  showed,  it  seemed. 

Kidneys. — Marked  pigmentation  of  the  convoluted  tubules  is  found. 

Lungs. — There  is  marked  tedema  and  moderate  congestion.  In  the 
capillaries  one  finds  a  few  megalokaryocytes. 


RANSOHOPf  MEMORIAL  VOLUME 


Experiment  E :    Rabbit   \' 
given  by  stomach  tube. 


Female.     Weight,   1,900  grams.      Pyrodi 


Date 

R.  P..  C. 

\V.  11. 

C.           Hb. 

Pyro.liM 

Remarks 

1906 

16-X 

5,500,()0() 

8.200 

61%    (.Mi.-scI 

K-r)     (Mil 

17-X 

5,sai,coo 

8.240 

62% 

(1,02 

18-X 

4,330,000 

9,760 

57% 

(l.(L' 

19-X 

4,310,000 

6,240 

48% 

(•.035 

2a-x 

3,425,000 

none 

22-X 

2,055,000 

23-X 

1,840,000 

9,280 

29% 

•• 

24-X 

2,105,000 

7,2CO 

.39% 

" 

25-X 

2.415.000 

5.680 

39% 

0.025 

26-X 

2,880,000 

7.760 

40%      •      " 

0.035 

27-X 

2,990,000 

6,000 

43% 

0.045 

29-X 

2.410,000 

7,360 

34% 

0.045 

31-X 

2,265,000 

6,320 

31% 

0.04 

1-XI 

2,735,000 

5,680 

3S% 

0.05 

2-XI 

2,600,000 

3,680 

29% 

0.03     Fresli    sol 

iition    of    pyrodin. 

3-XI 

2,5io,axi 

6.160 

26% 

0.04 

S-Xl 

2,585,000 

17.840 

29% 

0.04 

6-XI 

2,310.000 

5.600 

30% 

0.04 

7-XI 

2,660,000 

5.520 

35% 

0.045 

8-XI 

1,850,000 

9.000 

25% 

none 

9-xr 

2,070.000 

6,640 

30% 

O.M 

10-XI 

2,150,000 

5.280 

30% 

0.045 

12-XI 

2,275,0(X) 

7,040 

30% 

0.05 

13-XI 

2,090,000 

4,720 

26% 

none 

14-XI 

2,7.30.000 

8.720 

.34% 

0.07 

15-XT 

2,775,000 

5.760 

31% 

0.14 

Rabbit  was  found  dead  at  8  :00  a.  m.  Autopsy  at  1 1  :00  a.  m.  Rigor 
mortis  present.  Spleen  8.5  .x  1.5  .x  0.5  cm.  Right  lobe  of  liver  greatly 
atrophied.  Two  small  nodules  in  liver  and  the  normal  mottling  of  the  organ 
lost.  \'ery  small  amount  of  slightly  reddish  ascitic  fluid.  Otherwise  the 
findings  at  section  were  the  same  as  in  rabbit  I. 

MiCROscopicvL  Examination. — Bone  Marrozv. — Both  sections  and 
smears  show  myeloblastic  hyperplasia  of  the  bone  marrow. 

Spleen. — The  section  resembles  closely  that  from  rabbit  I\'.  A  few 
pseudoeosinophile  myelocytes  are  seen  in  the  meshes  of  the  jnilp  and  there 
are  a  few  megalokaryocytes.  There  are  small  nests  of  mononuclear,  non- 
granular cells,  which  look  like  lymphocytes,  in  the  venous  sinuses.  Smears 
of  the  spleen  show  many  lymphocyte-like  cells,  rarely  a  nucleated  red  blood 
cell,  and  a  few  myelocytes. 

Lh'cr. — There  is  some  cloudy  swelling  and  i)igmenlalion  of  the  liver 
cells.  No  nests  of  cells  are  to  be  seen  in  the  capillaries.  The  smears  are 
negative. 

Lungs  show  moderate  (edema.  There  are  no  megalokaryocytes  in  the 
capillaries. 

The  other  organs.  e-\cei)iing  the  kidneys  which  present  tiie  usual  changes. 
are  negative. 

Page  l,>0 


ROGER  S.  MORRIS 


Experiment  F  :  Rabbit  \'I.  Female.  Weight  (?) — average  size.  Pyro- 
din  given  by  stomach  tube. 

Date           R.  B.  C.           W.  B.  C.  Hb.             Pyrndiii                   Remarks 
1906 

16-X          4,090,000        8,080      61%  (Miesclier)     0.01 

17-X          4,705,000      11,640      60%  "    ■         0.02 

18-X          4,025.000        8,640      52%  "             0.02 

19-X          4.260,000      10.000      52%  "             0.0.35 

2n-X           .•^590  000  .Animal   weak. 

22-X          1,5.35,000  none 

At  about  10:00  a.  m.  on  October  23.  1906,  rabbit  died.  Autopsy  at  3:30 
p.  m.  The  organs  were  all  negative  except  for  marked  anaemia.  There 
was  very  little  fluid  blood.  No  bleeding  on  section  of  liver.  Clotted  blood 
in  heart,  arteries,  and  veins.  Bone  marrow  grayish  brown.  Spleen,  5  cm. 
long. 

Microscopical  ExAMiNATioN.^Bojir  Marrow. — The  fatty  marrow  of 
the  femur  is  largely  replaced  by  cellular  myeloid  tissue  in  which  there  are  a 
few  normoblasts  and  a  few  myelocytes,  the  majority  of  the  cells  being  non- 
granular mononuclears  (myeloblasts).  There  are  many  megalokaryocytes 
and  a  few  phagocytes.    Smears  reveal  nothing  additional. 

Spleen. — The  pulp  is  poor  in  cells.  The  capillaries  and  venous  sinuses 
are  greatly  widened  and  filled  with  blood.  The  follicles  are  slightly  di- 
minished in  size.  There  is  a  moderate  number  of  phagocytes.  A  few  very 
small  collections  of  mononuclear,  non-granular  cells  are  found  in  the  venous 
sinuses.  In  the  stnear.';  many  cells  resembling  the  myeloblasts  of  the  marrow 
are  present ;  there  are  very  few  myelocytes  and  no  normoblasts  seen. 

Liver. — There  is  nothing  unusual  with  the  exception  of  a  few  giant  cells 
in  the  liver  capillaries.  Smears  show  very  few  non-granular  mononuclear 
cells  like  those  seen  in  the  spleen ;  no  normoblasts  or  myelocytes  are  found. 

Kidneys. — Slight  cloudy  swelling  and  pigmentation  of  the  cortex. 

Lungs. — An  occasional  megalokaryocytic  embolus  is  to  be  seen. 

No  cause  can  be  found  for  the  rapidly  progressive  pernicious  course  of 
the  anaemia  in  this  case.  The  rabbit  received  exactly  the  same  doses  of 
pyrodin  (and  on  the  same  days  and  hours)  as  rabbit  V;  in  the  one  the  blood 
count  gradually  fell  till  exitus  lethalis  occurred  less  than  nine  days  after  the 
beginning  of  the  intoxication;  in  the  other  the  fall  in  the  number  of  the  ery- 
thocytes  was  less  pronounced  and  a  fatal  issue  did  not  result.  The  probable 
explanation  would  seem  to  be,  in  part  at  least,  defective  powers  of  hasma- 
togenesis  in  rabbit  \'I,  such  as  one  sees  in  the  so-called  aplastic  pernicious 
anaemia  in  man.  This  assumption  is  further  supported  by  the  practical  ab- 
sence of  nucleated  red  blood  cells  from  the  circulating  blood  during  the 
entire  course  of  the  anremia.  In  this  case  there  was  not.  however,  aplasia 
of  the  blood  forming  organs.  It  is  true  that  there  was  not  complete  myeloid 
transformation  of  the  fatty  marrow  of  the  femur,  and  evidence  of  hasma- 
topoiesis  in  the  spleen,  if  present,  was  slight,  but  it  is  uncertain  whether 
the  hyperplasia  of  the  blood  forming  organs  in  this  instance  is  any  less  than 
that  which  might  be  found  in  the  rabbit  ordinarily  after  an  acute  an.'emia 

Page  l/il 


UAX^OllOhl'  MJiMORIAL  VOLUME 


lasting  a  little  iiiuix-  than  eight  day,-.  Xu  alleratioiis.  ulher  than  those  char- 
acteristic of  pyrodin  poisoning,  were  found  in  any  of  the  organs,  and  there 
is,  therefore,  a  similarity  lietween  the  result  obtained  in  this  experiment  and 
certain  cases  of  "aplastic"  an.-emia  in  man,  for  in  the  latter  the  disease  pro- 
cess results,  it  seems  probable,  from  excessive  blood  destruction  with  little 
or  no  evidence  of  compensatory  blood  formation. 

The  earliest  attempt  at  studying  haniatopoiesis  in  anccmia  of  adult  ani- 
mals experimentally  was  made  by  Bizzozero  and  Salvioli  (3)  in  1881.  .\fter 
venesection  in  guinea-pigs  and  dogs  they  found  large  numbers  of  nucleated 
red  blood  cells  in  the  spleen,  which  normally  contains  few,  as  well  as  in  the 
bone  marrow.  In  rabbits,  whose  spleen  contains  no  nucleated  reds  normally 
in  adult  life,  they  were  unable  to  produce  changes  similar  to  those  obtained 
in  guinea  pigs  and  dogs.  They  believed,  as  a  result  of  their  experiments, 
that  the  spleen  was  active  in  regenerating  the  blood.  Later  Gibson  (4)  re- 
peated their  experiments  on  dogs  in  part,  with  the  same  result,  and  he  made 
ihe  observation  that  many  of  the  nucleated  reds  in  the  spleen  presented  divi- 
sion figures  in  the  nuclei,  a  point  strongly  in  favor  of  their  local  origin.  In 
1890,  there  appeared  the  work  of  Howell  (5),  in  which  he  was  able  to 
show  that,  after  severe  and  repeated  bleedings,  and  in  some  instances 
after  a  single  strong  hoemorrhage,  nucleated  red  blood  corpuscles  were 
demonstrable  in  the  spleen  of  the  cat  with  every  indication  that  they 
were  multiplying  there,  though  normally  these  cells  are  not  found  in  the 
cat's  spleen  in  postnatal  life. 

Ill  studying  the  spinal  cord  changes  occurring  in  experinienial  an;enii.i 
of  rabbits  produced  by  pyrodin,  von  \'oss  (6)  noted  that  there  was  a 
deposition  of  granular  pigment  in  the  spleen  with  areas  of  necrosis,  fatl\ 
degeneration  in  the  liver,  and  in  the  kidneys  all  stages  of  parenchyma- 
tous nephritis.  Tallquist  (7)  directed  his  attention  especially  to  the  iron 
content  of  the  organs  of  dogs,  in  which  both  acute  and  chronic  anaemia 
had  been  produced  by  the  administration  of  pyrodin  and  of  pyrogallol, 
and  was  able  to  prove  in  many  instances  a  marked  increase  in  the  iron 
of  the  liver  with  considerable  deposition  of  haemosiderin  in  the  spleen, 
kidneys,  and  bone  marrow  frequently.  In  my  own  experiments  there 
was  a  marked  reaction  for  hemosiderin  in  liver,  spleen,  and  kidneys  in  rab- 
bits I  and  II,  the  only  ones  in  which  it  was  tried,  but  the  equally  marked  pig- 
mentation of  the  cells  in  the  remaining  animals  makes  it  probable  that  the 
same  holds  true  in  all  six.  In  the  bone  marrow  in  my  cxpcrinieiits  the  pig- 
ment is  contained  chiefly  in  phagocytes.  In  only  one  instance  was  fatty  dc- 
degeneration  of  the  liver  found,  as  von  \'oss  reported,  while  in  none  of  my 
animals  were  the  renal  changes  sufficiently  marked  to  consider  the  existence 
of  a  nephritis.  \'ery  recently  Rothmann  and  Mosse  (8)  have  studied  the 
effect  of  chronic  pyrodin  poisoning  in  dogs  and  give  additional  results  of 
the  general  findings  at  autopsy  (Mosse).  No  changes  were  found  in  the 
lymph  glands.  The  spleen,  enlarged  at  autopsy  as  in  the  reports  of  all  jire- 
vious  workers,  contained  much  pigment  and  the  follicles  were  entirely  i)ro- 


ROGER  S.  MORRIS 


served.  The  characteristic  inilp  cells  were  not  well  preserved.  The 
kidneys  showed  the  usual  changes,  they  say,  in  the  epithelial  cells  of 
the  straight  and  convoluted  tubules.  HEemosiderosis  of  the  liver  was 
noted.  Most  interesting  was  the  condition  of  the  hyperplastic  loone  mar- 
row, similar  to  that  described  by  Reckzeh  (9)  in  dogs  after  jiyrogallol- 
ansemia.  The  cells  often  designated  ■"Stammzellen"  or  myeloblasts  were 
present  in  very  large  numbers,  there  were  many  normoblasts  and  few  granu- 
lar cells.  Unlike  others,  Reckzeh  described  megaloblasts  in  addition  to  nor- 
moblasts in  the  bone  marrow.  The  marrow  of  the  femur  in  my  ex])erinients 
showed  myeloblastic  hyperplasia  in  all  instances  with  the  exception  of  rab- 
bit III,  in  which  there  was  a  chronic  infection,  a  fact  which  may  explain 
the  large  numbers  of  granular  cells. 

Lastly,  and  of  greatest  interest  in  connection  with  the  jiresent  work. 
Hunting  (10)  in  1906  showed,  among  other  things,  that  chronic  ansemia  of 
rabbits,  produced  by  the  administration  of  saponin,  lead  in  some  instances  to 
collections  of  cells  in  the  venous  sinuses  of  the  spleen,  just  as  Meyer  and 
Heineke  had  found  in  man  and  as  I  found  in  my  first  two  experiments.' 
"The  peripheral  venous  sinuses  of  the  spleen  were  much  dilated  and  crowded 
with  cells  of  the  marrow  type  chiefly  of  the  erythrogenetic  series,  but  in- 
cluding many  megalokaryocytes  and  leucocytes.  The  nucleated  red  blood 
cells  were  grouped  much  as  in  the  marrow  and  showed  numerous  mitotic 
figures.  The  veins  of  other  organs  are  practically  free  from  nucleated  red 
cells,  except  for  an  occasional  small  group  in  the  liver  and  the  constant  pres- 
ence of  megalokaryocytic  nuclei  in  the  capillaries  of  the  lung."  In  Bunting's 
rabbits  the  anamia  did  not  become  very  severe,  and  this  he  attributed  to  tht- 
\acarious  blood  formation  occurring  in  the  spleen.  It  seems  much  more 
likely,  however,  that  in  some  way  tolerance  to  the  poison  was  established, 
for  in  my  first  experiment,  where  evidence  exists  of  hfematopoiesis  in  bone 
marrow,  spleen,  and  liver  as  well,  there  developed,  nevertheless,  a  profound 
anaemia  with  fatal  issue.  As  in  his  animals,  I  have  found  megalokaryoytes 
in  the  capillaries  of  the  lungs,  but  not  constantly.  They  were  not  present  in 
the  liver  capillaries  in  Bunting's  experiments. 

The  anaemia  produced  by  pyrodin  is  due,  not  to  any  interference  with 
normal  blood  formation,  so  far  as  is  known,  ])ut  to  a  great  increase  in  blood 
destruction.  Pyrodin  acts  upon  the  red  blood  cells  causing  shrinkage  and 
deformity,  and  as  Heinz  (11)  has  demonstrated,  these  effects  are  most  pro- 
nounced about  twenty-four  hours  after  the  administration  of  the  drug.  In 
my  experimental  animals  the  color  index  remained  high,  as  in  Tallquist's 
experiments.  Fortunately  in  the  present  work,  the  complete  blood  examina- 
tion was  made  always  between  twenty-two  and  twenty-four  hours  after  the 
administration  of  the  pyrodin.  The  changes  in  the  red  blood  cells  will  Ijc 
discussed  in  another  paper.  Suffice  it  for  present  purposes  to  say  ihat  the 
ileformities  in  the  red  blood  corpuscles  which  Heinz  described  occurred  in  all 
of  my  rabbits.     The  serum  was  examined  several  times  for  the  presence  of 

s Mentioned   in    the   prelimin-qry    report,  nt    Meyer   and    Heineke,    1905     )].    v. 


RANSOHOFF  MEMORIAL  VOLUME 


free  haemoglobin,  but  none  was  found,  an  experience  similar  to  Tallquist's, 
where  excessive  doses  were  not  employed.  Study  of  the  histological  sections 
shows  beyond  a  doubt,  it  seems,  that  the  injured  red  blood  corpuscles  are 
taken  u]>  by  phagocytes  which  are  found  in  very  large  number  in  the  spleen 
and  in  much  smaller  number  in  the  liver  and  bone  marrow.  In  a  very  short 
time  all  the  injured  cells  are  removed  from  the  circulating  blood,  unless,  pos- 
sibly, a  few  recover  and  are  able  to  functionate.  This  phagocytosis  of  red 
blood  cells  occurring  in  the  spleen,  liver,  and  bone  marrow  in  experimental 
animals  is  of  particular  interest  , since  Warthin  (12)  has  demonstrated  a  like 
occurrence  in  the  spleen,  lymph  glands,  hasmolymph  glands,  and  bone  mar- 
row in  pernicious  anremia  in  man.  We  have,  then,  produced  experimentally 
an  anaemia  which  may  be,  and  probably  is,  like  primary  pernicious  anaemia 
in  its  origin;  in  neither  is  there  hremoglobinaema,  as  a  rule,  though  this  may 
exist  exceptionally,  and  in  both  injured  red  blood  corpuscles  are  removed 
from  the  circulating  blood  by  phagocytes  found  in  the  haematopoietic  organs 
which  possess  the  double  function  of  forming  and  "cleaning"  the  blood. 

In  embryos  Kollicker  showed  many  years  ago — and  it  is  now  generally 
accepted — that  the  liver  is  the  chief  and  earliest  haematopoietic  organ. 
Later  in  foetal  life  the  spleen  also  assumes  this  function  and  finally  the  bone 
marrow  becomes  effective  in  blood  formation.  Toward  the  end  of  intra- 
uterine life,  and  in  the  early  part  of  post-natal  life  the  liver  and  spleen  cease 
forming  blood,  a  function  which  is  reserved  solely  for  the  bone  marrow.  As 
was  noted  before,  Ehrlich  has  shown  the  similarity  between  the  bone  mar- 
row of  the  embryo  and  that  of  many  patients  dying  of  pernicious  anaemia. 
And  Meyer  and  Heineke  demonstrated  a  like  analogy  between  the  blood- 
forming  liver  and  spleen  of  the  embryo  and  the  same  organs  in  pernicious 
anaemia.  They  have  also  called  attention  recently  to  a  further  point  of  re- 
semblance of  embryo's  blood  with  that  seen  in  ])ernicious  anjemia  in  the 
existence  of  a  high  color  index  in  each  and  elsewhere  I  shall  bring  forward 
still  another  analogy  in  the  presence  of  "Howell's  nuclear  particles"  in  the 
blood  of  the  human  embryo  and  in  that  of  pernicious  anaemia  in  man.  It  is 
evident,  therefore,  that  the  work  of  Meyer  and  Heineke  has  marked  a  dis- 
tinct advance  in  the  pathology  of  pernicious  anaemia,  in  that  they  have 
shown,  so  far  as  it  is  capable  of  demonstration  at  present,  that  there  is  not 
a  defective  regeneration  of  the  blood  in  pernicious  anaemia  (excepting  aplas- 
tic anjeniia),  but  rather  a  very  great  increase  in  blood  formation,  the  spleen 
and,  in  some  instances,  the  liver  assuming  this  function. 

In  the  present  experiments  it  is  not  possible  to  prove  absolutely  that  the 
liver  and  spleen  have  reverted  to  their  embryonic  condition  and  taken  up 
the  function  of  blood  formation,  but  it  is  possible  to  say  that  they  present  the 
histological  pictures  seen  in  the  liver  and  spleen  of  the  rabbit's  embryo  dur- 
ing the  stage  of  intrauterine  life  when  it  is  believed  that  these  organs  are 
actively  engaged  in  haematopoiesis,  and  the  inference  is,  therefore,  perfectly 
logical  that  their  function  is  the  same  here  as  it  is  during  fcetal  life.  That 
evidence  of  haematopoiesis  exists  in  the  spleen  in  practically  all  of  my  cxperi- 

Pagc  VA 


ROGER  S.  MORRIS 


ments  and  in  the  liver  in  (inly  one  instance  may  be  explained  by  the  fact  that 
the  spleen,  which  is  the  last  to  assume  its  blood-forming  power,  is  the  first 
to  regain  it,  whereas  the  liver,  beginning  its  hsematogenetic  function  at  an 
earlier  period  of  intrauterine  life  than  the  spleen,  reassumes  it  with  greater 
difficulty. 

COXCLUSIOXS. 

1.  The  anaemia  produced  in  rabbits  by  the  administration  of  pyrodin 
(by  stomach  tube  or  subcutaneously)  is  one  with  a  high  color  index  and  re- 
sults from  injury  to  certain  of  the  red  blood  corpuscles  which  are  then  re- 
moved from  the  circulating  blood  by  phagocytes  in  the  spleen,  bone  mar- 
row, and  liver.  This  resembles  the  condition  found  in  pernicious  anaemia 
in  man. 

2.  The  increased  blood  destruction  leads  to  increased  (compensatory) 
blood  formation. 

3.  The  stimulus  to  increased  regeneration  of  the  blood,  whatever  its 
nature  may  be,  leads  to  heightened  activity  of  the  hsematopoietic  function 
of  the  bone  marrow,  the  occurrence  of  myeloid  elements  in  the  spleen  and 
occasionally  in  the  liver. 

4.  The  changes  occurring  in  the  liver  and  spleen  in  the  experimental 
animals  are  similar  histologically,  so  far  as  the  haematogenetic  cells  are  con- 
cerned, to  those  seen  in  the  normal  rabbit's  embryo  at  certain  stages  in  its 
development,  and  it  may  be  assumed,  therefore,  that  the  spleen  and  liver 
have  taken  up  their  embryonic  function,  i.  e.,  haematopoiesis. 

5.  The  return  of  the  embryonic  function  is  in  the  reversed  order  of 
its  disappearance. 

6.  Haemosiderosis  of  the  organs  occurs  as  in  pernicious  anaemia  of 
man. 

7.  The  weight  of  experimental  evidence  favors  the  theory  of  increased 
blood  de,struction  ( the  toxic  theory )  rather  than  that  of  decreased  blood 
formation  as  the  chief  factor  in  the  production  of  primary  pernicious 
anaemia  in  man. 

For  illustrations  see  original  publication. 

REFERENCES. 

1.      Mevfi-   anil    IUmmIc        I  -  i.^  .     I  ;l  iiiljildi.nK   in    .Milz   iind   Leber   bei   schfeven   AnSmien       Vcv- 

hanill.   tl    ileiit^chen    i.ail i        l:.l     9.   i>.   22A.    1905. 

1  ■" ■    ?'lir'   Tl''l"'r'  '  '■    I'I'ilJnnR  bci  schwcren  Aniimien  und  Leukamien.     Deutsclles 

■'       lli/zciz!.!.!    and    ^     •     ^       l:   HI    LL-    zur    Hamatologie.      Molcschott's    Untersuchungen.    Bd.    2, 

'       '       ,   \         '    '     I'l ll.iinnni;    ciiKans    and    Blood-formation.      Jour,    of    .Nnat.    and    Pbysiol.. 

li...  1  ,,<■    l.ilV  lli^idiy   ,.f   the   Formed   Elements  of  tbe    Blood,    Especially  tbe   Red   Col- 

li. V.  \osM  .\natoniisclie  und  experimentelle  Untersuchungen  liber  die  Riickenmarltsveran- 
derun|,en   hei    Anamien.      Deutscbes   Arcliiv.    f.   klin.    Med.,    Bd.    58.    p     489.    1897. 

7.  Talldvist:     Ueber  expt-i  imentclle   Blntgift-Aniimieen.    Berlin.    19C0. 

8.  Rollimann  and  Mosse:  Ueber  Pyrodinvergiftnng  bei  Hunden.  Deutscbe  med.  Wochenschr.. 
Bd.    32,    p.    187,    191)6. 

9.  Reckzeh:  Ueber  die  dnrcb  das  Alter  des  Organismus  bedingten  Verscbiedenbeiten  der  ex- 
perimentellen    erzeugten    Blutgift-Anamieen.      Zeitscbr.    f.    klin.    Med..    Bd.-  54.    p.    1(j5.    1904. 

10.  Bunting:  Experimental  .\n:vmias  in  the  Rabbit.  lour,  of  Experimental  Med.,  Vol.  8. 
p.   625,    1906. 

11.  Heinz:  Morpbologische  Veranderungen  der  rotben  Blutkorperchen  durcb  Cifte.  Virchow's 
.Archiv.,   Bd.    122,   p.    112.    1890. 

ous   An.-tmia,    with    Special    Reference   to   Changes    Oc- 
Jour.    of   Med.    Sciences,    \-ol.    124,   p.    (,74.    1902. 


CLINICAL  CONSIDER. \TI().\  OF  OSTEOMYELITIS."^ 
A.  J.  OciisN-Ku,  .M.U..  LL.D..  F.A.C.S.. 

AND 

D.  \V.  Ckii.i:.  F..S..  M.D.. 
Chicaso. 

It  has  seemed  worth  while  to  consider  osteomyelitis  from  the  standpoint 
of  the  clinician  hecause  circumstances  have  favored  us  with  an  oppor- 
tunity of  ohserving  an  unusally  large  numljer  of  cases  suffering  from  thi- 
affliction. 

^Iv  observations  began  thirty-four  years  ago  when  1  served  as  assistant 
to  Professor  Moses  Gunn.  who  treated  a  very  large  number  of  these  cases. 
Following  his  death,  I  served  as  chief  assistant  to  Prof.  Charles  T.  Parkes 
for  a  period  of  three  years,  and  after  his  death  as  chief  assistant  to  Profes- 
sor Nicholas  Senn  for  a  period  of  four  years.  Each  of  these  surgeons 
had  a  great  number  of  cases  of  osteomyelitis ;  hence  my  sjiecial  interest  in 
this  subject. 

In  my  own  practice  at  the  Augnstana  Hosjjital  during  the  twenty  years 
from  Jaiuiary  1.  1S99.  to  January  1,  1919,  I  have  treated  301  cases  of 
osteomyelitis,  so  that  the  following  views  are  based  upon  the  treatment 
and  observation  of  a  sufficiently  large  number  of  cases  to  be  worthy  of 
consideration.  My  assistant,  D.  W.  Crile,  served  in  France  and  England 
for  a  period  of  three  years  during  the  recent  war.  where  he  had  an  oppor- 
tunity of  observing  several  thousands  of  cases  of  osteomyelitis  due  to  gun- 
shot and  shell  wounds,  and  he  likewise  is  interested  in  the  subject. 

Osteomyelitis  is  a  disease,  inflammatory  in  nature,  involving  bone  and 
having  its  origin  practically  always  in  the  medullary  tissue,  although  at 
times  it  may  originate  beneath  the  periosteum  (  1  ).  and  also  as  Lejars  (5) 
says:  '■Frequently  there  are  two  foci;  imp.  subperiosteal,  and  fine  in  the 
medulla." 

Osteomyelitis  may  Ije  subdivided  into  the  acute  infecti\e  tvpe,  the  sub- 
acute infective  (occurring  during  the  separation  of  sequestra  and  including 
rarifying  and  condensing  processes  in  the  bone),  and  chronic  osteomyelitis 
in  which  the  infecting  organism  determines  a  further  sulxlix  ision  into  pyo- 
genic, tuberculous,  or  syphilitic. 

As  a  matter  of  fact,  the  division  of  infective  osteomyelitis  into  an  acme, 
subacute,  and  chronic  stage,  is  purely  arbitrary,  and  often  can  be  accom- 
plished only  with  the  greatest  difficulty,  since  the  disease  is  a  progre.ssive 
one.  However,  as  a  general  rule,  the  acute  stage  may  be  said  to  occupy 
the  period  when  a  general  systemic  reaction  exists  characterized  by  fever, 
loxsemia,  an  increased  pulse-rate,  intensive  pain,  always  located  near  the 
affected  part  and  generally  being  dift'use  over  the  entire  neighborhood.  The 
subacute  stage  may  be  said  to  begin  when  the  tox?emia  has  been  overcome 


*  From  Surgeo'.  GynecoloRy  and  Obstetrics.   September.  1920. 
'  Read  before  the  Chicago  SurKical  Society,  February  6.   1920. 
Page   .}?« 


A.  J.  OCHSNIiR  AM)  D.  IV.  CHILE 


and  Mippmatiuii  still  exisl>.  The  chronic  stage  constitutes  that  ]ieriod  i:i 
which  the  bone  cavities  exist. 

It  is  possible  for  the  acute  stage  to  be  absent,  clinically,  so  that  when 
first  discovered  the  disease  may  be  subacute  or  it  is  possible  for  both  the 
acute  and  subacute  stages  to  be  negative  clinically  so  that  when  first  dis- 
covered, the  chronic  stage  exists.  This,  however,  is  due  to  the  fact  that 
the  early  stages  were  looked  upon  as  rheumatism,  growing  pains,  or  neu- 
ritis. 

Clinically,  the  tuberculou>  and  syphilitic  forms  should  occupy  a  sepa- 
rate classification.  They  are  cbrotiic,  although  each  may  be  subdivided  mh) 
an  early  and  a  late  stage  of  the  disease.  Their  course.  i)athology,  aud 
treatment  are  quite  different  from  that  of  the  pyogenic  forms  so  that  the\- 
will  not  be  considered  at  this  time. 

AX ATOMV 

The  disease  dejx-nds  for  its  location  and  characteristics  ujion  the  faci 
that  bone  is  a  rigid  and  peculiar  structure  composed  of  a  hard,  sparsely 
vascularized  cortex  and  a  soft  highly  vascular  core  (the  medulla),  and  i 
circumferential  vascular  covering,  the  periosteum. 

All  bones  contain  these  three  structures.  However,  they  are  present 
in  varying  proportions.  The  long  bones,  such  as  the  femur,  tibia,  fibula, 
humerus,  and  the  bones  of  the  forearm  contain  the  greatest  proportion  of 
hard  tissue  and  in  these  the  medulla  is  a  true  core.  This  core  is  trans- 
formed info  a  spread-out.  flat  structure  in  the  flat  bones,  but  occupies  the 
same  relative  position  to  the  cortex.  If  one  saws  through  a  bone,  the 
outer  layers  are  found  compact  while  the  medulla  is  found  to  be  cumpnsed 
of  an  interlacing  of  thin  spikes  and  spicules  having  attachment  to  the  cor- 
tex. The  ditterence  in  these  two  portions  is  pronounced,  the  cortex  beinj; 
composed  almost  entirely  of  solid  matter  while  the  medulla  contains  large 
spaces  between  the  spicules,  in  which  there  are  fat,  marrow  cells,  thin 
walled  blood-ves.sels,  and  a  considerable  amount  of  blood.  Ilowcxer,  close 
in.spection  shows  that  the  union  between  these  parts  is  not  an  abrupt  one 
and  that  it  is  often  impossible  to  say  at  what  point  the  marrow  becomes 
the  cortex.  Howexer,  in  the  femur  and  humerus  and  to  a  less  extent  in 
(he  tibia  a  definite  medullary  cavity  exists  in  adolescent  and  adult  life — the 
shaft  of  the  bone  being  hollowed  out  more  completely  than  the  ends.  This 
cavity  contains  true  medullary  tissue;  fat,  lymphoid  cells,  and  h;emoblastic 
centers.  On  breaking  a  long  bone  transversely,  one  is  able  to  .see  that 
even  the  densest  part  of  the  femur  is  pierced  by  tiny  canals,  each  contain- 
ing a  blood-vessel  and  the  larger  ones  containing  lymphoid  tissue.  These 
canals  are  smallest  in  diameter  directly  beneath  the  periosteum  where  they 
are  about  1/1000  of  an  inch  in  diameter  and  as  one  progresses  toward  the 
medulla,  they  gradually  increase  in  diameter  until  at  the  place  \vhere  the 
cortex  merges  into  the  medulla  they  are  about  1/200  of  an  inch  in  diameter. 
In  the  medulla  itself  they  attain  a  very  much  greater  size    (IKO-     These 


RANSOM  OFF  MEMORIAL  VOLUME 


canals  are  nothing  more  than  the  tubes  in  which  the  blood-vessels  lie  and 
are  called  haversian  canals  after  Clopton  Havers,  an  English  physician  of 
the  seventeenth  century.  Each  haversian  canal  is  surrounded  by  a  series 
of  concentric  columns  of  bone,  which  columns  are  divided  one  from  the 
other  by  concentric  rings  of  single,  little,  thread-like  processes  which  com- 
municate from  one  cell  to  the  other  and  with  the  central  tube  of  the  haver- 
sian canal.  These  cells  are  called  the  lacunse  and  their  thread-like  processes 
are  called  canaliculi.  The  concentric  layers  of  bone  which  are  really  fused 
into  one  column  and  the  adjoining  columns  which  are  fused  together  mak- 
ing a  continuous  plate,  are  called  lamellje.  Between  the  lamellae  and  between 
the  concentric  groups  of  lamellse.  one  finds  here  and  there  irregular  spaces 
which  evidently  are  a  result  of  the  absorption  of  hard  bone.  These  spaces 
are  called  haversian  spaces.  Virchow  (2)  says  that  each  of  the  cells  occu- 
pying the  spaces  between  the  lamellae  is  nucleated  and  Kolliker  (3)  is  au- 
thority for  the  statement  that  some  of  the  processes  from  these  cells  are 
connected  with  the  periosteum  and  undoubtedly  they  also  communicate 
freely  with  the  blood-vessels  of  the  haversian  canals. 

It  will  be  seen  from  this  survey  of  the  structure  of  bone  that  neither  the 
cortex  nor  the  medulla  should  be  considered  a  crystallized  or  an  inanimate 
substance.  As  a  matter  of  fact,  one  has  a  better  conception  of  the  true  na- 
ture of  bone,  if  he  considers  it  as  a  deposit  of  organized  mineral  salt  be- 
tween the  spaces  of  a  finely-branched  system  of  blood-vessels.  Not  only  is 
the  entire  bone  permeated  by  canals  containing  blood-vessels  and  living  cells 
absorbing  nourishment  from  these  blood-\essels,  but  lymphatics  also  most 
probably  exist  (4). 

The  periosteum  is  also  very  vascular  and  is  a  rather  coarse,  fibrous  mem- 
brane, particularly  where  it  afifords  tendinous  insertions.  It  can  be  divided 
microscopically  into  three  parts :  the  one  in  immediate  contact  with  the  cor- 
tex of  the  bone,  consists  of  strands  of  fibers  containing  quite  a  number  of 
granular  corpuscles,  particularly  in  the  young  animal.  These  corpuscles 
are  precisely  the  same  as  those  one  finds  bordering  the  haversian  canals, 
and  it  is  possible  that  they  are  similar  to  the  bone  corpuscles  found  in  the 
lacuna. 

Surrounding  this  division  of  the  periosteum  is  a  layer  of  elastic  fibers, 
and  the  outer  part  of  the  periosteum  again  becomes  composed  of  white, 
fibrous  strands  containing  many  blood-vessels,  which  ramify  and  prepare 
to  enter  the  openings  of  the  haversian  canals  of  the  cortex  before  they 
penetrate  the  elastic  layer  of  the  periosteum.  These  blood-vessels  in  the 
periosteum  appear  to  have  some  muscular  tissue  in  their  walls,  but  the 
vessels  which  enter  the  bone  are  devoid  of  muscle  (except  the  nutrient  ar- 
tery). The  blood  supply  of  the  bone  comes  also  from  nutrient  arteries 
which  gradually  enter  the  medullary  cavity  by  a  hole  running  obliquely 
through  the  compact  cortex,  and  in  the  long  bones  the  artery  generally 
enters  near  the  middle  of  the  shaft.  There  are  generally  a  few  nutrient 
arteries  entering  the  bones  near  their  ends,  but  for  the  large  part  the  fora- 

Page  ^SS 


A.  J.  OCHSNER  AND  D.  IV.  CRILE 


niina  which  one  ^ees  near  the  end  of  bones  are  for  the  emission  of  veins. 
There  arc  two  main  nutrient  arteries  for  the  femur. 

The  course  of  blood  lliroiigh  a  bone.  Arterial  blood  enters  a  bone 
through  two  routes,  the  most  evident  route  being  via  a  nutrient  artery 
which,  after  it  reaches  the  medulla,  sends  blood  both  up  and  down  the 
bone,  rapidly  dividing  into  an  arborization,  the  branches  of  which  are  short, 
emptying  quickly  into  comparatively  large  venous  spaces.  The  other  route 
of  arterial  blood  is  via  the  periosteal  vessels,  the  arborization  having  already 
occurred  in  the  periosteum — when  following  this  route  the  arteries  are  lost 
track  of  almost  immediately  and  capillary  vessels  conduct  the  blood  through 
the  haversian  canals  in  which  it  may  be  said  to  become  venous  at  once.  It 
seems  that  this  periosteal  blood  penetrates  a  very  little  distance  into  the 
bone,  compared  to  the  distance  that  the  medullary  prenutrient  supply  does. 
One  can  readily  see  how  this  comes  about  when  one  remembers  that  the 
haversian  canals  have  their  smallest  diameter  near  the  circumference  of 
the  bone.  The  blood  issuing  from  the  cut  surface  of  live  bone  alwavs 
exhibits  the  characteristics  of  venous  flow,  except  when  the  nutrient  artery 
itself  is  cut.  For  these  reasons  arterial  blood,  on  entering  the  proper  bony 
circulatory  system,  loses  much  of  its  impulse  and  becomes  static.  One  may 
compare  the  entrance  of  l)lood  into  a  bone  with  that  of  the  entrance  of  a 
stream  of  water  into  a  tank. 

Eoci  of  infection.  Therefore,  any  organisms  contained  in  the  blood  and 
brought  by  the  blood  to  a  bone,  find  their  first  opportunity  to  rest  at  the 
point  where  they  enter  the  interosseous  circulation.  This  point  may  be 
either  directly  beneath  the  periosteum  or  in  the  medulla  at  the  point  where 
the  branches  of  the  nutrient  artery  enter  a  blood-space.  With  the  stasis 
of  the  blood,  the  bacteria  settle  and  begin  to  multiply,  undisturbed  by  a 
blood  current.  In  this  way  bacteria  which  are  not  virile  enough  singly  or 
two  or  three  together  to  make  a  home  for  themselves  in  a  more  active 
tissue,  are  enabled  to  begin  an  infective  process  in  the  bone.  Having  multi- 
plied to  sufiicient  numbers,  they  excite  a  little  inflammation  in  the  delicate 
cells  lining  the  blood  space.  These  cells  swell  and  leucocytes  and  fibrin 
accumulate,  shutting  off  this  blood  space  from  the  remainder  of  the  cir- 
culatory system.  This  can  occur  easily  because  bone  encloses  the  blood 
space  in  all  directions  except  its  entrance  and  exit,  so  that  swelling  must 
occur  only  toward  the  cavity  of  the  space  and  can  not  occur  circumferen- 
tially.  From  this  little  focus  toxins  and  young  bacteria  disseminate,  repro- 
ducing and  extending  this  same  process.  We  know  that  this  is  true  from 
clinical  experience,  because  the  primary  focus  in  acute  osteomyelitis  is 
practically  always  in  the  shaft  and  corresponds  with  the  arborization  of 
the  nutrient  artery  as  a  general  rule,  occurring  most  frequently  at  the 
places  where  stasis  is  greatest,  e.  ;/..  on  the  dia[)hyseal  side  of  the  epiphyseal 
lines  and  at  the  cortex  of  tiie  bone.  .At  both  these  places  the  blood-vessels 
are  narrow,  and  the  blood  current  \ery  sluggish. 

It  is  true  that  in  many  cases  there  seems  to  be  a  simultaneous  involve- 


RAA-SOHOl'F  MEMORIAL  VOLUME 


ment  of  tht  Mibperiosteai  region  and  the  niedulla.  bin  while  thi.s  is  pos- 
sible it  seems  most  hkely  that  the  i)roce>s  begins  in  one  or  other  of  these 
locations  and  rapidl)-  extends  through  the  communicating  blood  spaces  from 
the  medulla  to  the  subperiosteal  region,  or  vice  versa.  Lejars  has  noted 
the  frequency  of  this  occurrence  and  advises  that  whenever  an  accumula- 
tion of  pus  is  found  beneath  the  periosteum,  it  should  be  opened  widely, 
even  though  no  other  indication  exists — for  a  medullary  abscess  is  im- 
dout)tedly  present. 

ilACTHKlOLOtiV 
Almost  an\-  organism  may  be  found  in  osteomyelitis.  By  far  the  large 
majority  of  cases  are  due  to  the  ])resence  of  the  ])yogenic  cocci  (6).  and 
the  staphylococcus  is  the  organism  most  frequently  found.  Streptococcus 
in  all  its  strains,  the  typhoid  bacillus,  the  pneumococcus,  the  colon  bacillus, 
the  Klebs  Loeffler  bacillus  and  others,  have  all  been  found  in  this  disease, 
so  that  it  is  quite  evident  that  the  disease  is  not  dependent  on  a  specific 
organism.  Neither  is  there  any  proof  that  any  particular  strain  of  or- 
ganism exercises  a  selective  action  for  the  Ixme  marrow  . 

IXCIDKXCK  01--  DISl'-.A.sl-; 

(Jsteonixelitis  occurs  most  frequently  in  the  adolescent  boy.  In  a  series 
of  104  cases  at  the  Copenhagen  Hospital,  it  \\as  found  that  boys  were 
affected  three  times  as  frequently  as  girls,  thai  tin-  liones  were  affected  in 
the  following  order:  femur,  39;  tibia.  ,M  and  Innncrus.  9;  fibula.  7;  radius. 
4  and  ulna.  2.     (  )ur  ex])erience  confirms  this  sequence. 

It  is  interesting  to  note  the  greater  frequency  of  the  femur  since  this 
bone  has  more  nutrient  arteries  entering  it  than  any  of  the  otiier  long 
bones.  The  long  bones  are  much  more  frequently  involved  than  any  of  the 
others.  The  infrequent  incidence  of  acute  infectious  osteomyelitis  in  the 
vertebr;e  is  interesting  when  compared  with  the  incidenci-  of  tuberculosis 
of  the  vertebrae,  and  in  this  connection  we  would  like  lo  point  out  that 
perhaps  there  are  many  cases  of  the  disease  in  this  region  which  are  in- 
correctly diagnosed  until  spinal  meningitis  is  manifested  and  as  -nch  prove- 
fatal. 

There  is  no  doubt  that  trauma  i>redisposes  to  the  localization  of  the 
condition  at  the  site  of  bony  contusion.  This  is  the  true  explanation  of 
the  greater  frequency  of  the  disease  in  boys,  although  the  latter  are  also 
more  subject  to  exposure. 

The  disease  often  follows  exanthemalous  fevers,  typhoid  fever,  pneu- 
monia, acute  pleurisy  or  the  presence  of  a  hidden  focus  of  infection  any- 
where in  the  body.  \\'hen  following  these  diseases  it  is  plainly  the  result 
of  a  haematogenous  transportation  of  the  germ.  It  is  believed  that  the 
presence  of  infected  tonsils,  infected  teeth,  disease  of  the  middle  ear  or 
sinuses,  or  chronic  appendicitis,  are  often  responsible  for  the  origin  of  the 
bacteria   causing   this   clisca^e.      in    its   acute   stage,   it    sometimes   is   only   a 


A.  J.  OCHSNER  AM)  P.  IV.  CHILE 


manifestation  of  a  septicemia  or  a  iJVjeiiiia,  aiul  in  these  most  serious  con- 
ditions, multiple  foci  often  exist.  Ho\\e\cr.  the  disease  does  not  neces- 
sarily indicate  this  grave  condition. 

PATHOI.oC.N 

Early  in  the  acute  attacks  the  medulla  i-  congested  centerin,s(  ahnut  the 
focus  of  infection.  The  periosteum  oxerlying  the  involved  region  is  hy- 
persemic,  pinkish  in  color,  and  heavy  with  cedema.  It  feels  tense  and  ruh- 
bery,  but  there  is  no  actual  j)itting  as  one  sees  accompanying  inflammation 
in  the  subcutaneous  tissues.  On  separating  the  periosteum  from  the  bone, 
bleeding  is  more  evident  than  it  is  in  the  normal  condition,  indicating  that 
the  tiny  blood-vessels  which  enter  the  haversian  canals  from  the  periosteum 
are  dilated  in  their  attemiJt  to  carry  an  extra  amount  of  blood  to  the  in- 
jured area.  One  notices  this  hy])era?niia  in  the  cortex  itself  in  some  cases 
when  the  marrow  cavity  is  opened,  for  the  congestion  is  quite  marked.  The 
normal  fat  tissue  which  ordinarily  will  not  flow  has  a  melted  appearance 
and  oil  may  even  be  seen  oozing  from  the  marrow  spaces.  At  this  incipient 
stage  one  may  find  no  pus  whatever,  and  it  is  during  this  time  that  opera- 
tion accomplishes  the  most  good,  since  if  the  medulla  is  well  drained  at  this 
time,  the  infection  may  be  checked  absolutely  so  that  medullary  and  cor- 
tical necrosis  do  not  occur  at  all.  One  may  discover  this  stage  on  the  first 
or  second  day,  but,  as  a  general  rule,  abscesses  are  present  within  twenty- 
four  hours  of  the  onset.  The  abscess  centers  about  the  initial  infarct  and. 
if  not  seen  until  considerable  pressure  has  been  developed  in  the  medulla, 
secondary  aljscesses  will  be  found  often  at  c|uite  a  distance  from  the  primary 
focus.  It  is  not  at  all  uncommon  to  find  the  entire  medulla  of  the  bone 
full  of  pus.  At  this  stage  of  the  disease,  which  may  be  encountered  at  any 
time  after  the  first  twelve  hours,  one  fre(|uently  finds  subperiosteal  ab- 
scesses as  .well,  which  have  developed  from  the  medulla  tlirough  the  ha\er 
sian  canals  to  the  subperiosteal  region  or  \  ice  versa. 

Epiphysitis. — The  epiphysis  becomes  invohed  in  12  to  15  pVr  ceiu  of 
the  cases  and  between  the  second  and  seventh  day  of  the  disease.  When 
the  epiphysis  does  become  involved  further  growth  of  bone  from  the  epi 
physis  may  be  arrested  particularly,  if  actual  separation  has  occurred. 

As  a  general  rule,  the  disease  is  limited  to  the  diaphysis,  the  epiphyseal 
cartilage  acting  as  a  block  against  extension  of  the  process  into  the  joints. 
And  also  the  close  adherence  of  the  periosteum  at  the  epiphyseal  lines 
checks  the  extension  of  subperiosteal  suppuration  towards  the  joints.  This 
in  counter-distinction  to  the  characteristics  of  tuberculosis.  However,  the 
joints  proximal  to  the  acute  infection  commonly  show  distention,  the  dis- 
tending fluid  being  a  protective  outpouring  of  lymph  into  the  synovia,  and 
the  fluid  in  these  joints  is  very  seldom  infected.  At  times  this  fluid  max 
even  show  traces  of  blood  and  the  synovia  are  oedematous  and  hyperremic. 

Sequestration. — After  frank  jnis  has  appeared  in  the  medulla,  one 
hardly  expects   to  prevent   llie  necrnvi^   which   generally    follow-   o>teomye- 


RAXSOHOFF  MEMORIAL  VOLUME 


litis.  The  inflaniinatory  pressure  which  develops  simultaneously  with  pus 
in  tiie  bones  causes  a  shutting  oft'  of  the  blood  and  nourishing  lymph  to 
certain  parts  of  the  involved  bone.  Thus  these  parts  die,  and,  after  varying 
lengths  of  time,  are  separated  from  the  living  parts.  The  separation  of  the 
delicate  medullary  bone  occurs  more  quickly  than  does  cortical  sequestra- 
tion. Thus  medullary  sequestra  may  be  loosened  after  two  weeks,  while 
the  cortical  sequestra  generally  take  from  four  to  eight  weeks  in  separating. 
The  separation  seems  to  be  accomplished  through  the  activity  of  certain 
marrow  cells  termed  osteoclasts  whose  function  it  is  to  destroy  all  unneces- 
sary bone.  However,  it  seems  that  the  presence  of  pus  itself  has  some  solv- 
ent action  upon  dead  bone  and  this  action  is  demonstrated  by  the  gradual 
disappearance  of  small  sequestra  which  are  constantly  bathed  in  pus.  This 
solution  of  sequestra  is  a  long  and  slow  process  which  may  be  aided  by 
chemical  stimulation,  but  surgical  removal  of  sequestra  after  separation  is 
our  practice. 

Character  of  Pus. — As  the  acuteness  of  the  process  decreases,  the  char- 
acter of  the  pus  changes  gradually,  until  in  the  subacute  and  chronic  stages 
the  pus  becomes  a  thin,  serous  fluid  lacking  the  milky  rich  appearance  of  the 
pus  found  in  the  acute  condition.  The  very  initiation  of  the  process,  how- 
ever, is  generally  accompanied  by  a  very  thin,  almost  clear  exudate,  and  this 
is  particularly  true  when  the  offending  organism  is  the  streptococcus. 

Rcfair. — Reparative  processes  begin  sinniltaneously  with  the  formation 
of  sequestra  which  may  be  single,  multiple,  or  the  entire  shaft  may  become 
a  sequestrum.  Inflammation  stimulates  the  bone-producing  mechanism,  and 
it  is  not  long  until  new  bone  begins  to  appear  beneath  the  periosteum.  It 
seems  that  this  does  not  come  from  the  periosteum  itself  but  from  bone 
element  left  clinging  to  the  periosteum  and  nourished  by  the  ves.sels  of 
the  periosteum.  After  three  or  four  weeks,  the  periosteum  begins  to  have  a 
brittle  feel  much  like  the  crackling  of  delicate  tissue  paper,  and  gradually 
the  layer  of  new  bone  nourished  by  the  periosteum  assumes  a  definite  thick- 
ness and  gradually  loses  its  property  of  being  molded  until  after  eight  or  ten 
weeks  a  definite  shell  of  new  bone  surrounds  the  old  dead  bone.  This  new 
involucrum  is  poor  in  quality.  It  is  honeycombed  with  spaces  through  which 
pus  escapes  from  the  neighborhood  of  the  enclosed  sequestrum  or  sequestra. 
There  may  be  only  one  small  hole  through  the  involucrum  but  where  mul- 
tiple sequestra  are  contained,  many  cloaca  are  found  and  often  the  new 
shell  ot  l)one  is  so  fenestrated  as  to  resemble  a  very  imperfect  lattice  work. 

Tiie  new  involucrum  may  be  very  imperfect  in  its  reproduction  of  the 
original  bone.  Particularly  is  this  the  case  when  entire  portions  of  the  shaft 
have  been  destroyed  and  the  limb  has  not  been  kept  in  its  normal  shape  by 
orthopedic  appliances.  This  most  often  occurs  in  the  upper  arm  and  thigh 
since  in  these  parts  there  is  only  a  single  bone.  In  the  leg  and  forearm  where 
a  second  bone  generally  retains  its  shape,  deformity  does  not  so  readily  occur. 

New  bone  is  also  formed  from  the  medullar}-  region,  but  this  bone  is 
not  so  imi)ortant  pathologically  since  from  its  position  it  can  not  surround 


A.  J.  OCHSNER  AND  D.  W.  CRILE 


dead  fragments,  and  therefore  is  more  homogenous  and  of  better  quality 
than  is  the  subperiosteal  bone. 

Granulation  tissue  is  more  generally  found  growing  from  the  medullary 
region  than  from  the  periosteal  region,  and  it  seems  that  the  chief  efforts 
from  the  core  are  directed  toward  the  removal  and  destruction  of  sequestra 
and  bacteria,  while  the  efforts  of  the  circumferential  tissues  seem  to  be  di- 
rected toward  the  reproduction  of  supporting  bone.  So  far  as  the  pathology 
of  the  chronic  stage  is  concerned,  it  makes  no  diiTerence  whether  the  acute 
process  has  been  cut  short  by  surgical  intervention  or  whether  nature  has 
accomplished  the  overthrow  of  the  acute  infection.  In  either  case  the  suc- 
cessful outcome  will  have  been  accompanied  by  the  creation  of  an  exit  for 
the  pus,  so  that  in  the  later  stages  one  sometimes  finds  sinuses  leading  from 
the  sequestra  to  and  through  the  skin.  If  these  sinuses  are  the  result  of 
the  spontaneous  evacuation  or  of  insufficient  incisions  through  the  perios- 
teum in  draining  the  abscesses  they  may  be  very  long  and  devious.  An  ab- 
scess arising  in  the  medulla  at  one  end  of  a  bone  may  not  find  egress  from 
the  interior  of  the  bone  until  it  reaches  a  point  quite  a  distance  from  its 
origin.  Here  it  breaks  through  the  cortex  to  the  subperiosteal  region,  where 
it  may  travel  still  further  from  the  original  focus  before  it  makes  exit 
through  the  periosteum  into  the  fascial  planes  overlying.  This  is  most 
likely  to  occur  near  the  insertion  of  a  tendon  and  from  this  point  the  pus 
generally  travels  along  the  tendon  sheath  toward  the  surface  where,  after  a 
superficial  abscess  is  formed,  rupture  occurs.  Frequently  the  spontaneous 
sinus  has  a  direct  course  to  the  surface  and  when  this  is  true  it  resembles 
the  sinus  resulting  from  surgical  drainage.  In  either  event  the  sinus  in  the 
chronic  stages  is  lined  by  granulation  tissue.  The  granulations  which  spring 
from  the  interior  of  the  involucrum,  together  with  those  that  line  the  sinus, 
pour  out  a  thin  chronic  discharge.  Often  the  deeper  granulations  assume 
characteristics  which  have  led  French  writers  to  call  them  "fongosites." 
These  "fongosites"  are  overgrown,  poorly  nourished,  oedematous  masses — 
when  cut  they  do  not  bleed  as  healthy  granulation  tissue  does.  They  have  a 
sickly  gelatinous  appearance  and  almost  always  indicate  the  presence  of  a 
sequestrum.  When  the  sequestrum  has  been  dissolved,  discharged,  or  re- 
moved, the  cavity  of  the  involucrum  fills  slowly  and  incompletely  with  these 
granulations  depending  from  the  lining  membrane  of  pseudo  periosteum. 
These  involucral  cavities  persist  for  great  lengths  of  time  and  seldom  fill 
in  with  healthy  tissue.  As  time  goes  on  the  involucrum  becomes  very  dense, 
and  this  is  particularly  true  where  there  have  been  multiple  small  cavities 
and  sequestra  while  the  bone  at  a  little  distance  suffers  an  atrophy.  These 
two  conditions  may  be  seen  in  the  same  bone  or  one  or  the  other  may  be 
present  alone.  The  sclerotic  condition  is  termed  condensing  osteitis  while 
the  other  is  rarifying  osteitis. 

The  pathology  of  the  chronic  condition  which  wc  iiave  described  is  gen- 
erally absent  altogether  following  thorough  primar\'  surgical  interference, 
but  these  changes  are  so  frequently  present  they  must  be  described. 

I'a.jc  !,.U 


RA.VSOHOFF  MEMORIAL  VOLUME 


In  considering  the  pathology  of  this  condition,  one  must  also  remember 
that  the  overlying  soft  parts  may  suffer  changes  dependent  upon  infection, 
disuse  or  deformity,  and  likewise  contiguous  joints  may  suffer  from  actual 
infection  or  secondary  reactions. 

SYMPTOMS 

Intense  pain  is  the  most  striking  symptom  of  acute  osteomyelitis — pain 
so  severe  that  the  patient's  perception  of  one's  intention  to  touch  the  limb 
elicits  agonizing  shrieks.  In  severe  cases  the  vibration  of  a  bed  from  people 
walking  nearby  causes  pain  and  the  slightest  motion  of  the  affected  limb  is 
intolerable.  The  pain  may  be  preceded  by,  but  generally  precedes,  a  high 
fever,  a  rigor  or  a  succession  of  rigors,  general  toxaemia,  and  sweating. 
Soon  the  affected  limb  becomes  swollen,  heavy,  and  inflamed;  the  swelling 
is  generally  diffuse,  as  when  the  femur  is  involved  the  whole  thigh  becomes 
tense,  red  and  tender.  In  the  leg  or  forearm  the  oedema  is  apt  to  be  most 
pronounced  over  the  aft'ected  bone.  The  joints  are  usually  not  swollen  nor 
tense  in  the  first  few  hours,  but  may  rapidly  fill  with  serum  and  result  in  the 
appearance  of  an  arthritis;  in  these  cases  the  limb  ma}-  be  held  in  the  typical 
positions  of  the  various  arthritis. 

The  temiJerature  rises  acutely  to  very  high  levels,  103°  to  105°.  and  is  of 
a  continuous  type  with  little  variation  between  morning  and  evening.  The 
patient  is  generally  unable  to  sleep.  The  pain  is  not  definitely  localized  but 
involves  the  entire  limb.  The  pain  becomes  worse  on  lowering  the  limb, 
as  one  would  expect  since  in  this  position  congestion  is  increased,  and, 
therefore,  pressure  on  the  nerves  is  increased. 

When  the  bone  is  involved  subcutaneous  tapping  on  it  at  a  distance  from 
the  focus  will  cause  pain  at  the  involved  area.  In  case  of  an  abscess  or 
before  an  abscess  is  formed,  induration  may  be  found  over  the  site,  par- 
ticularly when  the  subperiosteal  focus  is  present. 

In  the  less  acute  type  the  pain  is  of  a  constant  character,  described  as  an 
aching,  located  in  the  bone,  and  resembling  the  so-called  growing  pains. 
These  cases  occasionally  show  a  slight  febrile  reaction,  present  one  day  and 
absent  for  an  interval.  Sometimes  the  patient  will  refuse  to  use  the  limb 
as,  after  use,  the  pain  increases.  The  subacute  type  may  or  may  not  be 
jiainful.  There  is  generally  an  occasional  spell  of  fever  with  malaise  in  the 
part.  This  spell  may  be  precipitated  by  changes  in  the  weather  or  over- 
exertion.   The  surface  of  the  bone  may  show  nodules  and  irregularities. 

The  chronic  type  without  sinuses  is  seldom  di.scovered  in  boys  and  girls 
and  in  older  j>eople  often  simulates  and  is  probably  diagnosed  as  chronic 
rheumatism.  It  is  this  type  that  includes  the  circumscribed  bone  abscess 
and  bone-cysts.  The  chronic  stage  of  the  acute  disease  is  almost  always 
made  evident  by  the  presence  of  a  discharging  sinus. 

D1.\G.\0SIS 
Acute   infective  osteomyelitis  must  be  dift'erentiated   from   acute   rheu- 
matic fe\er  which  can  usually  be  accomplished  by  noting  that  the  affection 

Pane    Mi 


A.  J.  OCHSNER  AND  D.  IV.  CRILE 


is  extra-articular.  When  cuntigiious  joints  are  swollen  secondarily,  how- 
ever, the  differentiation  is  not  easy.  When  this  condition  exists,  tapping 
over  the  bone  at  a  point  farthest  from  the  joint,  may  cause  pain  in  the  bone, 
while  in  an  acute  rheumatic  joint,  such  tapping  may  be  painless  unless  the 
joint  be  moved.  The  presence  of  a  single  synovitis  argues  against  acute 
rheumatism.  One  finds,  too,  that  the  skin  overlying  the  joints  is  less  red 
and  redematous  when  the  synovitis  is  secondary  to  osteomyelitis.  The  gen- 
eral prostration,  while  it  may  be  great  in  both  the  diseases,  is  often  greater 
in  osteomyelitis.  Sometimes  the  joint  contiguous  to  the  osteomyelitic  bone 
can  be  moved  painlessly,  but  this  is  rare ;  one  must  always  dift'erentiate  be- 
tween acute  osteomyelitis  and  an  early  stage  of  infantile  paralysis.  At 
times  this  is  very  difficult.  The  presence  or  absence  of  stiffness  of  the  neck 
is  very  important  in  this  differentiation,  and  whenever  two  limbs  are  in- 
volved one  can  safely  rule  out  osteomyelitis,  as  the  disease  rarely  begins 
with  a  double  focus  except  as  evidence  of  a  general  pyaemia.  The  acute 
arthritis  of  infants  generally  occurs  in  the  hips  and  knees  and  is  most  often 
found  in  nursing  babes  and  may  be  associated  with  a  gonorrheal  ophthalmia 
or  vaginitis  (8).  In  very  young  children  one  must  always  bear  in  mind 
the  possibility  of  the  presence  of  scurvy,  which  can  be  readily  recognized  be- 
cause it  affects  many  joints. 

Acute  arthritis  deformans,  especially  when  occurring  in  children,  may 
be  very  difficult  to  differentiate.  Generally  the  arthritis  is  multiple,  how- 
ever, the  prostration  not  nearly  so  sudden,  the  temperature  not  nearly  so 
high,  and  the  joints  less  tense.  All  these  conditions,  however,  can  be  ex- 
cluded by  the  exact  localization  of  the  process  outside  the  joint,  and  gener- 
ally on  the  diaphyseal  side  of  the  epiphysis.  The  condition  should  not  be 
overlooked  in  its  earliest  state  when  it  is  usually  considered  a  strain  or  sprain 
or  contusion,  since  a  history  of  trauma  is  frequent. 

The  X-ray  is  of  little  or  no  value  in  the  diagnosis  of  the  early  acute  stage 
except  in  a  negative  way,  since  it  may  confirm  the  presence  of  periosteitis, 
tuberculous  or  syphilitic  disease,  or  fractures;  when  medullary  abscess  for- 
mation has  occurred,  an  excellent  X-ray  plate  may  demonstrate  the  condi- 
tion, but  the  diagnosis  should  be  confirmed  by  one  who  is  thoroughly  fa- 
miliar with  the  shadows  seen  in  this  condition,  since  they  are  often  very 
faint  and  illy  defined.  The  later  stages  of  the  disease  when  bone  cavities, 
cysts  and  sequestra  exist  are  readily  detected  by  the  X-ray. 

PKOG.XOSIS 

The  prognosis  of  the  acute  disease  is  always  grave.  When  death  occurs 
it  is  generally  during  the  acute  condition,  and  one  finds  pyaemia,  infarcts  in 
lungs,  kidneys,  liver,  brain  and  vegetative  conditions  of  the  circulatory  sys- 
tem as  well  as  multiple  foci  of  infection.  These  conditions  may  be  the 
result  of  an  unattended  asteomyelitis,  but  often  are  concomittant  evidences 
of  hjematogenous  infection  from  some  common  area. 

Early  diagnosis  with  immediate  surgical  treatment  modifies  the  gravity 

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RANSOHOFF  MEMORIAL  VOLUME 


of  the  condition  considerably,  but  one  should  never  predict  that  a  limb  with 
unimpaired  function  may  result. 

Often  when  the  focus  is  virulent  and  extensive  and  early  treatment  has 
been  neglected,  when  the  general  reaction  is  extreme  (the  type  of  case  which 
appears  to  have  been  "hit  by  a  sledgehammer"),  amputation  has  been  recom- 
mended as  offering  the  best  hope  of  recovery.  In  our  experience  this  ex- 
treme measure  has  never  seemed  indicated,  although  patients  have  frequently 
been  sent  to  Augustana  hospital  for  this  last  hope.  In  these  cases  it  has 
always  been  possible  to  change  the  condition  by  laying  open  the  periosteum 
and  overlying  soft  tissues,  applying  an  enormous  hot  moist  boric  acid  and 
alcohol  dressing  covered  with  a  large  rubber  cloth  which  serves  the_  pur- 
pose of  retaining  heat  and  moisture  and  at  the  same  time  acting  as  a  splint, 
and  by  applying  a  therapeutic  lamp  over  this  dressing.  In  a  small  group 
of  very  severe  cases  it  is  advisable  not  to  chisel  open  the  medullary  cavity 
of  the  bone  at  the  primary  operation. 

With  early  and  thorough  surgical  drainage  one  may  not  expect  the 
process  to  spread  into  the  neighboring  joints,  even  though  synovitis  already 
exists  in  them.  When  the  focus  is  close  to  the  epiphyseal  line,  separation 
of  the  epiphysis  may  follow  with  the  resultant  loss  of  the  power  of  growth 
from  that  end  of  the  bone. 

At  times  the  extreme  virulence  of  the  disease  results  in  the  destruction 
of  the  osteogenetic  powers  of  the  tissues  so  that  the  bone  will  not  regene- 
rate. Rarely,  the  opposite  result  obtains,  /.  e.,  bony  overgrowth  follows  the 
chronic  type. 

With  early  surgical  intervention  witliin  the  first  few  hours  of  the  dis- 
ease and  in  the  absence  of  pyaemia,  the  focus  being  well  away  from  the 
epiphyseal  line,  one  may  expect  recovery  with  a  functioning  limb  even  in 
extremely  serious  cases  after  a  long  period  of  disability  and  with  the  re- 
mote prospect  of  several  secondary  operations  for  the  removal  of  sequestra 
and  for  the  obliteration  of  the  sinuses. 

TREATMENT 

Acute  infectious  osteomyelitis  does  not  seem  to  have  been  recognized 
until  comjjaratively  recent  times,  the  explanation  probably  being  that  the 
abscesses  finding  their  way  to  the  surface,  obscured  the  deep  pathology 
and  the  cases  were  treated  simply  as  very  grave  attacks  of  boils. 

The  treatment  of  the  acute  condition  so  commonly  practiced  until  re- 
cently with  poultices,  blisters,  fomentations,  sedatives,  cupping,  antipyretics, 
salves  and  ointments  or  manipulation  and  the  healing  arts,  should  be  most 
heartily  condemned.  The  only  proper  method  of  treatment  is  surgical 
drainage,  splitting  and  reflecting  of  periosteum  over  the  entire  distance 
and  at  least  two  centimeters  beyond  and  on  each  side,  and  opening  the 
medullary  cavity  freely  in  the  area  involed.  Combined  with  or  follow- 
ing this,  ilie  i)art  should  be  immobilized  by  splints  so  arranged  that  dress- 
ings can  be  done  without  disturbing  the  splint.     Fomentation  in  the  form 

Page  .(36 


A.  J.  OCHSNER  AND  D.  IV.  CRILE 


of  hot  moist  dressings  seems  a  valuable  adjunct  to  this  procedure,  and  any 
of  the  above  mentioned  remedies  may  be  emi)loyed  as  accessories  without 
harmful  effect  except  treatment  by  manipulation.  The  use  of  therapeutic 
lights  over  the  limb  is  a  very  valuable  adjunct  to  drainage  as  they  supply 
heat  without  the  necessity  of  disturbing  the  limb.  It  also  seems  that  the 
heat  waves  produced  by  means  of  electric  light  are  more  penetrating  than 
those  produced  by  the  application  of  ordinary  fomentations,  hot  water  bags 
and  electric  jiads. 

OPERATJOX 

The  patient  is  anesthetized,  the  limb  is  cleaned  and  painted  with  tinc- 
ture of  iodine.  The  incision  is  made  down  to  the  periosteum  avoiding 
arterial  regions  and  the  nerve-trunks  and  placing  the  incision  so  that  it 
will  drain  in  a  dependent  fashion  without  pocketing.  The  periosteum  is 
freely  incised  in  a  longitudinal  direction,  and  if  it  is  not  already  separated 
from  the  bone  by  the  presence  of  a  subperiosteal  abscess,  it  is  raised  by 
scraping  it  from  the  bone  by  a  sharp  rugine  such  as  Oilier  devised.  The 
blunt  periosteal  elevator  should  not  be  used  nor  should  the  periosteum  be 
stripped  roughly  from  the  bone.  A  sharp,  thin-bladed  chisel  serves  the 
purpose  admirably,  handled  with  great  accuracy  and  gentleness. 

Rough  treatment  would  result  in  leaving  the  osteogenetic  elements  on 
the  bone  and  would  leave  the  periosteum  impotent  to  produce  new  bone. 
A  hole  is  now  made  through  the  cortex  with  a  trephine  or  a  drill  or  by 
chisel  and  mallet,  great  care  being  taken  to  avoid  undue  jarring  of  the 
bone  before  the  operation  is  begun  or  during  the  operation.  It  may  be 
necessary  to  make  several  holes  through  the  cortex,  although  this  is  rarely 
necessary  if  the  point  of  greatest  tenderness  is  carefully  located.  In  the 
very  early  stages  one  may  find  no  frank  pus  whatever  but  the  marrow  will 
be  oily,  serous  and  oedematous-looking.  When  this  condition  or  the  pres- 
ence of  pus  is  discovered,  a  large  slab  of  cortex  should  be  removed,  leaving 
the  remaining  bone  in  the  shape  of  a  trough.  One  should  chisel  sufficient 
cortex  away  in  both  directions  from  the  focus  that  he  may  be  sure  that  no 
secondary  focus  remains  undrained. 

The  further  advantage  of  this  procedure  is  that  any  incipient  focus,  too 
early  to  be  detected  grossly,  will  be  nipped  in  the  bud  and  will  not  progress 
to  a  destructive  stage.  The  marrow  or  the  exposed  area  should  be  removed 
with  a  curette  and  the  walls  of  the  cavity  remaining  may  be  washed  with 
an  antiseptic  solution.  For  this  purpose  carbolic  acid  (5  per  cent)  seems 
ery  efficacious.  In  virulent  infections,  pure  carbolic  acid  may  be  used,  ap- 
plied on  a  cotton  swab  and  allowed  to  remain  from  two  to  five  minutes. 
After  this  time  it  should  be  diluted  with  alcohol  and  the  cavity  thoroughly 
washed  out  with  alcohol  (95  per  cent).  In  jilace  of  using  carbolic  acid, 
alcohol  alone  may  be  used  or  ether  may  be  used,  and  of  late  Dakin's  solu- 
tion has  come  into  favor  for  this  purpose.  Tincture  of  iodine  is  excellent. 
The  use  of   various  antiseptic  pastes  does  not   seem   so  successful   in  the 

Paac   -).^7 


RANSOHOFF  MEMORIAL  VOLUME 


treatment  of  ilie  acute  stai;;e.  although  the  bismuth,  iodine,  paraffin  paste 
seems  to  have  a  favorable  effect.  The  cavity  may  be  packed  with  iodoform 
gauze  or  plain  gauze  to  prevent  the  accumulation  of  a  blood  clot  after 
operation.  The  presence  of  clots  during  the  acute  stage  is  dangerous  and 
may  lead  to  continued  suppuration.  The  use  of  Carrel's  treatment  seems 
to  give  good  results.  Stewart  and  McCurdy  declare  that  3^4  per  cent 
iodine  is  the  best  antiseptic  and  that  packing  interferes  with  the  forma- 
tion of  a  blood  clot,  in  this  way  interfering  with  bone  repair.  It  is  most 
likely  that  the  cases  in  which  a  blood  clot  is  desirable  are  not  at  all  the 
type  of  case  that  we  are  considering  since  the  presence  of  lilood  clot  in 
this  class  of  cases  almost  invariably  leads  to  further  septic  developments. 
The  wound  is  left  open. 

Rosenberg  says  that  streptococcus  and  pneumococcus  epiphyseal  sup- 
puration often  heals  spontaneously  and  that  the  treatment  in  nursing  in- 
fants should  be  limited  to  the  opening  of  abscesses  (10).  He  may,  how- 
ever, have  confused  the  acute  arthritis  found  in  infancy  with  an  acute 
osteomyelitis.  One  should  hesitate  in  making  a  diagnosis  of  osteomyelitis 
in  suckling  infants  for  this  reason.  In  my  own  cases  of  osteomyelitis  in 
infants  the  results  have  been  amazingly  good  following  simple  incision. 

It  seems  that  Lejars  and  Robert  LeConte  (11)  agree  that  it  is  never 
expedient  to  incise  the  periosteum  only,  but  that  in  all  cases  of  periosteitis 
in  the  adolescent,  it  is  wise  to  expose  the  medulla.  If  no  medullary  pus 
is  found  little  harm  has  been  accomplished,  while  if  a  medullary  focus 
has  been  neglected  great  harm  may  ensue.  My  experience  has  borne  out 
this  plan  except  in  the  very  violent  cases  described  above  (A.  J.  O.) 
LeConte  favors  the  early  removal  of  all  bone  and  marrow  involved  and 
says  that  regeneration  will  occur  if  operation  has  been  done  early.  This 
corresponds  with  the  work  done  by  E.  H.  Nicholls,  of  Boston  (12),  who, 
writing  in  1904,  thought  that  the  periosteum  itself  deposited  new  bone 
after  this  operation.  There  can  be  no  doubt  that  new  bone  is  generally 
of  good  quality,  reproducing  the  shape  and  function  of  the  bone  which 
has  been  removed.  This  is  particularly  true  before  the  ossification  of  the 
epiphyses.  The  bone-forming  elements  which  iremain  attached  to  the 
periosteum  are  very  active  at  this  time  of  life.  It  would  seem  that  in 
order  to  understand  these  results,  one  must  believe  that  inflammation  of 
the  bone  loosens  the  bone-forming  elements  from  the  periosteum. 

Our  observations  have  convinced  me  that  it  is  never  proper  to  remove 
the  shaft  of  a  bone  during  the  acute  stage  of  osteomyelitis  before  an  in- 
volucrum  has  been  formed,  because  the  resulting  arms  and  legs  have  been 
infinitely  superior  in  all  cases  where  there  has  been  a  late  removal  of  the 
sequestra. 

Based  on  the  experience  of  handling  many  thousand  cases  of  trau- 
matic osteomyelitis  during  the  great  war,  it  would  appear  that  when  com- 
plete subperiosteal  excision  of  a  section  of  shaft  is  done  within  a  few 
hours   of    inoculation,   regeneration   occurs   with   more   difficulty   and   more 

Page  .',38 


A.  J.  OCHSNER  AND  D.  IV.  CRILE 


often  fails  to  occur  than  if  the  same  operation  is  performed  later.  In 
traumatic  osteomyelitis,  excision  of  a  section  of  shaft  bone  after  inflam- 
mation has  manifested  itself  by  congestion  and  thickening  of  the  peri- 
osteum, is  hardly  ever  followed  by  failure  of  regeneration  by  the  forma- 
tion of  subperiosteal  callus.  This  is  particularly  true  where  the  bone- 
scraping  technique  of  Oilier  has  been  followed  as  described  by  Leriche 
(13).  When  this  technique  has  been  skillfully  employed,  even  before  the 
periosteum  is  inflamed,  regeneration  almost  invariably  occurs.  These  facts 
argue  that  the  scraping  of  the  bony  cortex  and  inflammation  in  the  same 
region  result  in  leaving  bone-forming  elements  adherent  to  the  periosteum. 

This  explanation  of  the  question  makes  it  clear  that  subperiosteal  re- 
sections of  bone  in  acute  infectious  osteomyelitis  are  not  to  be  feared  pro- 
\'ided  operation  is  never  performed  in  this  condition  before  the  appear- 
ance of  inflammatory  symptoms.  This  simple  fact,  /.  c.  that  inflammation 
always  preceded  operation  in  this  condition  explains  the  regenerations  whicii 
Nicholls  so  fortunately  enjoyed  but  which  he  attributed  to  the  periosteum 
itself. 

The  work  of  Nicholas  Senn,  on  the  other  hand,  based  on  the  classical 
experiments  of  McEwen  (14).  gave  remarkably  favorable  results.  He  did 
not  favor  the  excision  of  the  entire  shaft  at  an  early  stage,  but  advocated 
the  operation  providing  radical  drainage,  leaving  a  shell  of  bone  to  be  dealt 
with  as  indicated  at  a  subsequent  operation.  Nicholls  agrees  with  this  idea 
when  the  disease  is  located  in  either  the  femur  or  the  humerus,  since  these 
bones  can  not  be  excised  without  considerable  deformity  and  shortening  re- 
sulting. In  the  case  of  one  of  the  bones  of  the  leg  or  forearm,  its  fellow 
serves  to  maintain  the  length  and  shape  of  the  limb  so  that  this  element  does 
not  enter  into  the  question  so  seriously  as  it  does  in  the  thigh  and  arm. 
Taking  all  things  into  consideration,  it  seems  that  the  best  treament  of  the 
initial  stage  of  the  disease  is  immediate  incision  through  the  periosteum, 
thorough  exposure  of  the  medulla,  leaving  enough  supporting  cortex  to  pre- 
vent deformity  and  in  such  a  shape  as  not  to  interfere  with  drainage  and 
leaving  a  layer  of  bony  scales  adherent  to  the  reflected  periosteum,  the  dis- 
infection of  the  exposed  tissues  with  tincture  of  iodine,  the  packing  of  the 
cavity  with  iodoform  gauze  to  be  removed  on  the  second  or  third  day,  and 
the  provision  of  free  dependent  drainage. 

This  treatment  should  be  instituted  immediately  on  making  the  diagnosis. 
One  must  be  careful  to  avoid  the  epiphyseal  cartilages  in  doing  the  opera- 
tion, since  injury  to  this  area  results  in  a  hindrance  to  further  bone-growth 
from  the  injured  end  of  the  bone.  When  the  infective  process  itself  involves 
the  epiphysis  there  is  no  other  course  to  adopt,  except  that  of  thoroughly 
clearing  away  all  diseased  tissue,  since  if  the  surgeon  be  hindered  by  timidity, 
it  is  possible  for  the  process  to  extend  into  the  contiguous  joint,  when  ampu- 
tation may  result.  It  is  wise  to  mention  the  possibility  of  the  subsequent 
shortening  which  one  anticipates  so  that  the  patient  and  his  relatives  may 
know  what  to  expect. 

Page    l.TO 


RAXSOHOFF  MEMORIAL  VOLUME 


Supplementing  this  operative  treatment,  tlie  limb  should  be  immobilized 
and  local  heat  supplied,  either  as  fomentation  with  hot  boric  acid  and  alcohol 
dressings  or  by  using  an  incandescent  lamp  so  arranged  that  its  heat  is  di- 
rected on  to  the  limb,  or  a  combination  of  the  two  methods,  the  lamp  tend- 
ing to  maintain  the  heat  of  the  moist  dressing.  The  patient  should  be  freely 
purged,  and  for  this  purpose  castor  oil  excels  all  other  drugs.  The  patient 
should  be  given  an  abundance  of  good  water  to  drink,  and  often  by  giving 
water  in  the  form  of  lemonade,  aerated  waters,  mineral  waters,  or  weak 
tea.  larger  amounts  may  be  drunk  than  if  only  plain  water  were  offered. 
Large  amounts  of  water  provoke  a  diuresis  and  this,  coupled  with  the 
purging,  tends  to  increase  the  excretion  of  the  toxins  which  the  patient  has 
absorbed  from  the  diseased  bone.  With  this  treatment,  the  infection  is 
rapidly  overcome  and  no  further  extension  of  the  process  should  occur. 

The  after-treatment  consists  in  the  remoxal  of  the  gauze  packing  on  the 
second  or  third  day,  or  sooner  if  the  temperature  does  not  fall  the  day  after 
operation.  It  is  seldom  necessary  to  insert  rubber  drainage-tubes,  if  the 
case  has  been  diagnosed  and  operated  on  in  the  early  hours  of  the  disease. 
However,  if  the  case  has  not  reached  the  surgeon  until  the  entire  medullary 
cavity  is  filled  with  frank  pus.  or  even  after  the  pus  has  begun  to  burrow 
in  the  soft  parts,  it  is  wise  to  remove  the  packing  after  twelve  to  twenty- 
four  hours  and  to  replace  it  by  one  or  several  drainage  tubes,  and  this  type 
of  case  will  do  very  well  when  treated  by  Carrel's  method,  with  frequent 
irrigations  through  many  fine  tubes,  each  one  leading  down  to  the  bone  cav- 
ity. The  wound  should  be  kept  open  while  it  heals  by  granulation  from 
the  depths.  It  is  occasionally  possible  to  suture  these  wounds  at  their  pri- 
mary operation,  leaving  a  corner  of  the  wound  open  to  pertnit  removal  of 
the  gauze  pack  and  for  the  insertion  of  a  drainage  tube,  if  necessary.  If 
doubt  exists  as  to  the  wisdom  of  closing  the  wound  at  once,  it  should  be  left 
wide  open  and  closed  at  a  second  operation  after  healthy  granulation  tissue 
appears.  This  should  be  postponed,  however,  until  the  wound  has  become 
free  from  infection,  which  can  be  determined  by  examining  the  secretion 
microscopically.  One  must  bear  the  fact  in  mind  that  the  presence  of  bac- 
teria is  proof  of  infection,  but  that  the  absence  of  bacteria  microscopically 
is  not  sufficient  evidence  to  prove  that  a  wound  is  sterile. 

The  cases  which  are  not  seen  by  the  surgeon  until  actual  necrosis  of  a 
section  of  the  shaft,  or,  for  that  matter  the  entire  shaft,  present  greater 
difiticulty.  It  is  in  these  cases  that  immediate  excision  of  the  necrotic  bone 
should  never  be  practiced. 

I  have  been  impressed  with  the  importance  of  this  rule  many  times  in 
cases  in  which  it  seemed  impossible  to  have  any  portion  of  the  shaft  of  a 
long  bone  restored  to  normal.  In  these  cases  we  employed  the  treatment 
described  above  of  splitting  all  of  the  soft  tissues  longitudinally  down 
through  the  periosteum  for  a  distance  of  two  to  five  centimeters  beyond  each 
end  of  the  area  apparently  infected  and  elevating  the  periosteum  from  its 
attachment  to  the  bone  for  a  distance  of  one  centimeter  each  side  of  this  in- 


A.  J.  OCHSNER  AND  D.  W.  CHILE 


cision  and  then  applying  hot,  moist,  boric  acid  and  alcohol  dressings  and 
])lacing  a  therapeutic  lamp  over  all.  It  has  been  surprising  in  many  of  these 
cases  how  small  the  total  loss  of  bone  has  been  ultimately.  The  bone  which 
seemed  hopelessly  dead  in  many  instances  seemed  to  act  in  the  capacity 
of  a  bone  graft,  being  replaced  to  the  greatest  extent  by  new  bone  so  that 
ultimately  only  a  very  small  portion  of  the  bone  was  lost. 

In  one  case,  a  girl  of  fourteen,  in  whom  the  attack  was  unusually  vio- 
lent, an  incision  over  the  entire  dorsal  surface  of  the  first  metatarsal  bone 
showed  this  structural  black  from  end  to  end  ready  to  be  removed  entirely. 
The  treatment  described  above  was  employed  and  in  twelve  weeks  the 
wound  was  completely  healed  without  the  loss  of  any  portion  of  the  bone. 
The  entire  bone  served  as  a  bone  graft.  The  healing  has  been  permanent. 
In  my  experience  this  observation  has  never  been  repeated  to  the  same 
extent  but  a  sufficient  amount  of  bone  has  been  saved  in  a  large  number 
of  cases  to  convince  me  that  much  value  should  be  placed  on  this  plan  of 
treatment. 

The  important  point  to  be  gained  comes  from  the  fact  that  this  treat- 
ment directs  the  lymph  stream  away  from  the  substance  of  the  bone  so 
that  there  can  be  no  advancement  of  the  pathologic  process,  while,  on  the 
other  hand,  all  of  the  natural  forces  can  proceed  with  the  work  of  restora- 
tion. 

Whatever  can  not  be  repaired  by  nature  can  be  accomplished  surgically 
later  on  at  leisure  when  the  patient  has  recovered  from  the  acute  condition 
and  when  the  element  of  sepsis  has  been  eliminated  and  the  surgeon  has  to 
deal  only  with  end-results  of  the  disease. 

CHROXIC  OSTEOMYELITIS 

The  experience  of  the  war  has  been  of  great  value  in  furnishing  ex- 
perience in  the  treatment  of  chronic  osteomyelitis,  although  conditions  are 
not  exactly  parallel.  The  important  lesson  universally  learned  corresponds 
with  the  experience  of  the  few  civilian  surgeons  who  had  a  large  experince 
with  chronic  osteomyelitis  before  the  war,  namely :  (  1  )  that  in  order  to 
succeed  one  must  remove  absolutely  all  dead  substance.  In  war  surgery 
this  means  foreign  substances  in  addition  to  sequestra  which  are  alone  to  be 
considered  in  civil  practice.  (2)  Provision  must  be  made  for  filling  the 
defect  after  all  foreign  bodies  and  dead  bone  has  been  removed  and  every 
portion  of  the  remaining  cavity  has  been  throughly  freed  from  infectious 
material. 

Methods  of  closing  the  defect.  My  earliest  experience  with  these  cases 
was  as  an  assistant  of  Moses  dunn,  in  whose  clinic  we  treated  a  great  num- 
ber of  cases  of  chronic  osteomyelitis. 

After  removing  all  sequestra  and  producing  a  smooth  cavity  he  tried  to 
obtain  healing  from  the  bottom  by  keeping  tlie  external  wound  open  l)y  means 
of  a  paraffin  plug. 


RANSOHOFF  MEMORIAL  VOLUME 


This  plan  ])roved  very  satisfactory  although  somewhat  tedious.  I  also 
had  an  opportunity  of  observing  many  cases  treated  in  the  clinic  of  Charles 
T.  Parkes  who  was  my  surgical  chief  following  the  death  of  Professor  Gunn. 
'IMie  same  plan  of  treatment  and  the  good  results  continued. 

For  a  number  of  years  following  this  experience,  I  assisted  Nicholas 
Senn  in  the  treatment  of  many  of  these  cases.  After  thoroughly  removing 
all  sequestra  and  infectious  matter  and  smoothing  the  cavity  in  the  bone,  he 
chiseled  away  a  sufficient  portion  of  the  involucrum  to  permit  the  edges  of 
the  wound  to  unite  without  the  slightest  tension. 

Then  the  cavity  was  carefully  disinfected  with  5  per  cent  carbolic  acid 
and  throughly  dried ;  then  finely  cut,  decalcified  bone  chips,  which  had  been 
preserved  in  1:1000  corrosive  sublimate  solution,  were  dried  and  sprinkled 
wilii  iodoform  powder  and  carefully  packed  into  the  ca\ity  in  sufficient 
quantity  to  fill  the  cavity  barely  full.  Then  the  edges  of  the  wound  were 
carefully  sutured  so  that  the  coaptation  was  perfect.  A  very  large  dressing 
and  immobilization  splints  completed  the  operation.  The  results  were  ex- 
cellent. The  reason  why  the  method  has  not  received  more  extensive 
adoption  lies  in  the  fact  that  few  surgeons  work  with  sufficient  accuracy  to 
carry  out  every  detail  of  this  procedure  which  is  necessary  in  order  to  pre- 
vent the  breaking  down  of  the  implanted  graft.  Moreover,  the  simpler 
method  introduced  by  Max  Schede  about  the  same  time  brought  identical 
results.  Moorhof  introduced  a  plug  about  the  same  time  which  we  used 
with  equally  good  results  in  a  few  cases  but  which  we  abandoned  again 
because  the  results  seemed  no  better  than  with  Schede's  method. 

This  method  consists  in  the  steps  described  in  connection  with  Senn's 
method  to  the  point  of  filling  the  cavity,  the  technique  then  being  as  follows : 

The  cavity  is  left  empty  and  the  wound  is  closed  by  means  of  a  double 
row  of  continuous  catgut  sutures  the  first  row  acting  as  tension  sutures  and 
the  second  row  as  coaptation  sutures.  An  Esmarch  constricting  bandage 
is  left  undisturbed  until  the  very  large  dressing  supported  with  a  number  of 
splints  has  been  applied  and  the  patient  has  been  returned  to  his  bed  with 
the  limb  elevated  in  order  to  prevent  the  cavity  to  fill  moderately  with  a 
blood  clot  which  may  remain  undisturbed  because  of  the  character  of  tli,' 
dressing  until  it  has  become  throughly  organized. 

In  each  of  the  three  methods  described  last  the  element  of  absolutely 
preventing  any  disturbance  of  the  clot  filling  the  cavity  in  the  bone  is  of  the 
very  greatest  importance.  The  failure  to  appreciate  this  fact  has  resulted 
in  most  of  the  bad  results  following  the  use  of  these  methods. 

In  cases  in  which  there  is  not  sufficient  tissue  to  cover  the  cavity  the 
method  described  by  Emil  Beck  of  carrying  what  skin  is  available  toward 
the  bottom  of  the  cavity  without  tension  has  given  very  satisfactory  results. 

In  a  number  of  cases  in  which  the  healing  has  been  too  slow,  we  have 
covered  the  granulating  surface  with  Thiersch  grafts.  It  is  amazing  to  see 
how  these  troughs  will  fill  up  after  covering  the  granulations  with  Thiersch 
grafts.     Occasionally  we  have  loosened  long  later;il  flajis  and  have  united 


A.  J.  OCHSNER  AND  D.  W.  CRILE 


these  in   front  over  the  defect  in  the  bone  and  then   we  have  covered  the 
defects  on  each  side  by  means  of  Thiersch  grafts. 

RECURRENCE 

In  our  cases  recurrence  has  seemed  to  be  due  most  commonly  to  the 
fact  that  during  the  primary  treatment  the  source  of  infection  was  overlook- 
ed so  that  the  patient  sufifered  from  a  re-infection  rather  than  a  recurrence 
in  the  usual  sense  of  the  word. 

Many  of  these  patients  state  that  they  had  a  cold  or  a  sore  throat  or  a 
toothache  just  before  their  osteomyelitis  recurred.  Upon  making  a  careful 
examination  one  finds  a  buried  tonsil  containing  an  abscess  or  an  abscess  at 
the  root  of  a  tooth  or  some  other  focus  of  infection.  For  thirty  years  we 
have  removed  these  infected  tonsils  and  roots  of  teeth  in  many  cases  in  which 
recurrence  had  occured,  and  the  patient  has  repeatedly  remained  free  from 
trouble  for  a  number  of  years. 

Trauma  is  another  common  cause  of  recurrence.  Apparently  some 
slight  injury  determines  the  return  of  infection  to  a  Ijone  that  has  previously 
been  the  seat  of  osteomyelitis. 

Sugar.  Patients  consuming  large  quantities  of  sugar  are  subject  to  the 
developement  of  furuncles  and  carbuncles  and  occasionally  this  seems  to  be 
an  element  in  determining  the  occurence  of  recurrent  osteomyelitis. 

Cold  and  exposure.  We  have  seen  a  number  of  recurrences  following 
exposure  to  cold  and  wet.  In  these  cases,  however,  there  has  been  an  in- 
fection of  the  tonsils,  the  sinuses  or  the  air  passages. 

We  have  not  been  able  to  associate  osteomyelitis  with  the  occurence  of 
intestinal  disturbances  although  a  priori  one  would  suppose  that  this  might 
be  a  source  of  infection. 

CONCLUSIONS 

1.  An  early  concise  diagnosis  and  immediate  surgical  treatment  is  of 
the  greatest  importance. 

2.  The  operation  should  invariably  consist  in  splitting  the  periosteum 
for  a  distance  of  2  to  5  centimeters  l)eyond  the  area  of  pain  upon  pressure 
in  the  bone  in  each  direction. 

3.  The  periosteum  should  be  loosened  from  the  bone  for  a  distance  of 
1  to  2  centimeters  on  each  side  of  the  incision. 

4.  In  extremely  severe  cases  this  should  be  the  extent  of  the  primary 
operation. 

5.  In  less  severe  cases  ultimate  healing  can  be  hastened  by  carefully 
opening  the  medullary  canal  at  the  point  previously  located  because  of  pain 
upon  pressure. 

6.  Care  should  be  employed  to  prevent  traumatizing  the  tissues  by 
rough  chiseling. 

7.  Moist  hot  antiseptic  dressing  with  fixation  of  the  extremity  and  with 
the  use  of  electric  light  treatment  increases  the  comfort  and  facilitates 
healing. 

Page  !,l,f. 


RANSOHOFF  MEMORIAL  VOLUME 


8.  The  shaft  of  a  long  hone  should  never  he  removed  until  a  good 
involucruni  is  formed. 

9.  In  late  cases  or  in  secondary  operations  upon  cases  treated  as  ahove 
in  the  acute  stage,  every  ])article  of  dead  tissue  must  he  removed. 

10.  At  this  o]:)eration  some  defnnate  iilan  must  he  carried  out  to  facilitate 
closing  the  defect. 

11.  Skin  grafting  is  of  great  value  in  many  cases. 

12.  Local  foci  of  infection  such  as  abscesses  of  tonsils  or  teeth  or 
sinuses,  should  invariahly  he  eliminated  at  once  upon  undertaking  the 
treatment  of  patients  suffering   from  osteomyelitis. 

REKKRENTK.S. 

1.  Coplin:     Manual    of    Pathology,    p.    718, 
la.  Ouanin's    Anatomy,    Vol.    1. 

2.  Virchow :     De   periliori    o.'^sium    structuria,    p.    17,    Fig.    6. 

3.  Kolliker:     Wlirzl,.    Xat.    Zlschr.,    Vol.    I,    296. 

4.  Cruikshank:     Anatomy    of  the   Ahsorhing   Vessels. 

5.  I.ejars :     Urgent    Surgery,   pp.    550-554. 

6.  Delafield   and    Prudden :     Textbook   of   Pathology,    p.    886. 

7.  Alfred  C.  Wood:    Acute  osteomyelitis  in  children.      Penn.   M.  J., 

8.  Clement    Lucas:     Quoted  by   Sir   Wm.    Osier.     The   Principles   .ind    Pr: 

p.   378. 

9.  Powell:     Carbolic   acid   in   surgery.      Med.    Record.    1899,   Iv.    372. 

10.  Rosenberg:     Osteomyelitis  in  suckling  infants.     Muenchen.  med.    Wchn 

11.  Robert   LeConte:     Acute  inflammation  of  long  bones.      Boston   M.    &   .S 

12.  E.   H.  Nicholls:    J.  Am.   M.  Assn.,   1904. 

U.  R.    I.eriche:    Treatment  of  Fractures.      I'niv.   London   Press,   Ltd.,    1918 

14.  Nicholas  Senn. 


A  RAPID  METHOD  OF  PNEUMOCOCCUS  TYPING.* 

Wade  \V.  Oliver. 

nrooklyii. 

Dccausi.'  of  its  prognostic  value  and  also  because  it  is  necessary  for  s])e- 
cific  serum  theraj)}-,  a  number  of  methods  for  the  determination  of  pneumo- 
coccus  types  have  come  into  use. 

The  standard  methods  up  to  1917  are  reviewed  by  Blake,"  special  emphasis  hcinij 
placed  on  intraperitoneal  inoculation  of  the  mouse  with  washed  sputum  and  aRRlulinin 
and  precipitin  tests  of  the  peritoneal  exudate.  Avery  ^  reports  a  rapid  cultural  method 
for  the  determination  of  pneumococcus  types  in  lobar  pneumonia.  By  the  use  of  a 
meat  infusion  broth  with  I  per  cent,  glucose  and  5  per  cent,  rabbit  blood,  sufficient 
growth  usually  is  obtained  within  five  or  six  hours  for  precipitin  test  made  with  the 
clear  fluid. 

In  order  to  still  further  save  time,  Mitchell  and  Muns'  describe  a  method  for  de- 
tecting pneumococcus  precipitinogen  in  sputum,  5  c.c.  of  which  are  ground  in  a  small 
mortar  with  sand  until  a  paste  is  formed.  Then  10  c.c.  of  normal  salt  solution  arc 
slowly  added  and  stirred  into  the  mixture  and  after  three  or  four  minutes,  the  dis- 
solved sputum  is  pipetted  off,  the  solution  centrifugalized  at  2,2nO  revolutions  per 
minute  for  from  five  to  ten  minutes,  and  a  precipitin  test  made  with  the  clear  fluid. 

Krumweide  and  Valentine  ■*  suggested  a  coagulation  method  for  the  rapid  deter- 
mination of  precipitable  substances  in  the  sputum.  As  in  the  method  of  Mitchell  and 
Muns,  considerable  quantities  of  sputum  are  required,  a  decided  objection  against  the 
method  in  certain  cases  in  which  only  small  amounts  of  sputum  can  be  obtained.  From 
3-10  c.c.  of  sputum  in  a  test  tube  are  placed  in  boiling  water  until  a  "more  or  less  lirm 
coagulum  results.  The  coagulum  is  then  broken  up  with  a  heavy  platinum  wire  or 
glass  rod  and  saline  is  added.  Just  enough  saline  should  be  added  so  that,  on  subse- 
quent centrifuging,  there  will  be  sufficient  fluid  to  carry  out  the  test."  The  tube  is 
again  placed  in  boiling  water  for  several  minutes,  after  which  centrifugalization  is 
employed.  The  supernatant  fluid,  which  is  the  antigen,  is  then  floated  over  0.2  c.c.  of 
undiluted  antiserum.  "If  a  fixed  type  was  present  in  the  sputum,  and  should  the 
sputum  have  been  rich  in  antigen,  a  definite  contact  ring  is  seen  in  the  tube  containing 
the  homologous  serum.  With  sputums  less  rich  in  antigen,  the  ring  may  develop  more 
slowly  and  it  will  be  less  marked." 

The  test  that  I  describe  is  based  on  the  solubility  of  the  pneumococcus 
in  bile.  Taking  advantage  of  the  fact  that  in  a  typical  case  of  lobar  pneu- 
monia the  infecting  type  of  pneumococcus  is  often  found  in  predominating 
numbers  in  the  sputum  of  the  patient,  1  c.c.  or  less  of  such  sputum,  imme- 
diately on  its  receipt  in  the  laboratory,  is  stirred  in  sterile  salt  solution  and 
bile  added.  After  the  protein  has  gone  into  solution  in  the  bile,  the  mi.xture 
is  filtered  and  a  precipitin  test  is  immediately  made  with  the  filtrate.  The 
series  on  which  tiiis  test  was  used  comprises  twenty-five  cases.     On  an  aver- 

Keceived  for  publication  June  26,  1920. 

*  Fror.1  The  Journal  of  Infectious  Diseasc>s,  October,    1920. 

'Jour.   Kxper.  Med.,  1917,  2C,  p.  67. 

"Jour.  Am.  Med.  Assn.,   1918,  70.  p.   17. 

'Jour.  Med.  Res.,  1917-8,  37,  p.  3,19. 

•Park  and  Williams,  Pathogenic  .Micro-organisms,   li/JO,   p.   318. 


RAN  so  HUFF  MEMORIAL  VOLUME 


age,  the  time  for  effecting  a  t_vping  was  from  twenty  to  thirty  minutes.    The 
results  follow^ : 

Methods  U.mployed  and  P.neumococcus  Types 


Cases 

Pneumococcus  Types 

Rapid 

Precipitin 

Aver 

y's  Method 

Mouse 

! 

— 



— 

NeEative 

Ne 

Xe 

i 

— 

Ne 

irativc 
Eativf 

\ 

Ne 

4 

Ne 

Xe 

4 

3 

i                  >"e 

1 
Kativc 

_!. 

rativc 

XcKative 

— 

V^ 

native 

Xe 

ative 

(>lreptococeus1 

~ 

(streptococcus) 


We  note  that  four  cases  belong  to  type  1,  three  to  type  2,  three  to  type  3. 
and  eleven  to  type  4. 

A  direct  smear  of  the  sputum,  a  selected  fragment  of  sputum  being 
chosen,  is  stained  by  Gram's  method,  as  examination  of  sucli  a  smear  is  of 
distinct  value  in  determining  the  presence  of  the  pneumococcus  as  well  as 
its  relative  numbers  in  the  sputum.  Next  1  to  1.5  cm.  of  sputum  are  placed 
in  a  clean  test  tube  which  contains  a  glass  rod.  Normal  salt  solution  is  then 
added,  small  quantities  (0.1  to  0.2  c.c.)  being  added  at  a  time  and  vigorous 
stirring  w^ith  the  glass  rod  following  the  addition  of  each  portion  of  solution. 
After  from  0.5  to  0.8  c.c.  of  salt  solution  have  been  stirred  into  the  sputum, 
from  three  to  five  drops  of  undiluted  ox  bile  are  added  and  the  mixture 
thoroughly  stirred.  The  amount  of  salt  solution  to  be  added  is  dependent 
on  the  consistency  of  the  sputum,  the  endeavor  being  to  obtain  a  fairly 
homogeneous  specimen  of  a  sufficiently  fluid  nature  to  admit  of  filtration  or 
centrifugation.  The  tube  is  then  immediately  placed  in  a  water  balh,  in 
water  at  45  to  48  C.  for  ten  to  twenty  minutes,  which  suffices  for  solution 
of  the  pneumococci  by  the  bile.  The  fluid  is  then  immediately  filtered.  For 
filtration,  a  filter  paper  listed  as  '"Eimer  and  Amend  Best  White  FiUer  Paper 
Xo.  15"  has  been  employed.  The  filter  paper  mounted  preferably  in  a  small 
funnel  having  a  long  stem,  is  first  moistened  with  a  small  amount  of  normal 
salt  solution.  Filtration  at  ordinary  atmospheric  pressure  will  usually  be 
somewhat  slow.  By  the  use  of  a  suction  pump  and  a  small  amount  of  nega- 
tive pressure,  the  process  of  fihration  is  greatly  facilitated.  It  has  been  my 
experience  that  the  filtrate  so  obtained  is  clear  and  colored  to  only  a  slight 
extent  bv  the  bile. 


IVADE  W.  OLIVER 


In  lieu  of  filtration,  centrifugilization  may  be  employed.  After  the 
pneumococcus  protein  lias  dissolved  in  the  bile,  the  mixture  is  placed  in  a 
centrifuge  tube  and  a  small  amount  of  cotton,  with  the  fibers  loosely  united, 
is  placed  on  the  top  of  the  fluid.  Centrifugalization  is  commenced  at  low 
speed  and  the  speed  is  gradually  increased  up  to  about  2,000  revolutions  per 
minute.  As  the  speed  increases  the  cotton  is  pulled  down  to  the  bottom 
and  assists  appreciably  in  clearing  the  solution. 

Of  the  filtrate  or  centrifiigate,  0.3  to  0.5  cm.  are  now  pipetted  into  each 
of  three  small  tubes.  To  the  first  tube  is  added  one  drop  of  undiluted  type  1 
pneumococus  antiserum,  to  the  second  tube  is  added  one  drop  of  undilute<l 
type  2  antiserum  and  an  equal  quantity  of  type  3  antiserum  is  added  to  the 
third  tube.  In  case  of  a  doubtful  reaction,  the  addition  of  another  drop  of 
antiserum  may  be  indicated. 

When  a  positive  precipitin  test  is  obtained,  a  clouding  occurs  in  tlie  fluid 
almost  immediately  on  the  addition  of  the  specific  antiserum.  The  test  be- 
comes still  more  marked  if  the  tubes  are  immersed  for  from  ten  to  twenty 
minutes  in  water  at  48  C.  Following  this,  if  the  tubes  are  placed  in  the 
icebox,  the  positive  tube,  after  several  hours,  will  show  a  sedimentation  of 
(he  specific  pneumococcus  proteid,  the  supernatant  fluid  appearing  clear. 

In  all  of  the  cases  in  which  a  positive  precipitin  test  for  one  of  the  fir^t 
three  types  of  pneumococci  was  obtained,  the  results  were  ideiUical  with 
those  obtained  by  the  Avery  method.  In  five  instances,  the  sputum  of  the 
same  patient  was  typed  on  several  consecutive  days,  with  identical  results, 
in  each  case  the  rapid  precipitin  test  checking  with  the  Avery  method.  In 
th^'fifteen  cases  in  which  the  rapid  precipitin  test  was  negative,  the  Avery 
method  revealed  a  type  4  pneumoocccus  in  eleven  of  the  series,  and  in  the 
remaining  four  cases,  a  streptococcus.  In  this  series  of  fifteen  negative 
tests,  intraperitoneal  inoculation  of  mice  with  washed  sputum  was  employed 
in  ten  and  in  each  instance  the  results  were  the  same  as  those  obtained  by 
the  Avery  method. 

The  necessity  of  obtaining  a  true  specimen  of  sputum  from  the  dee])er 
air  passages  as  free  as  possible  from  saliva  was  strikingly  brought  out  in 
case  8.  The  first  specimen  was  not  sputum,  but  saliva,  and  the  rajiid  pre- 
cipitin test  and  the  Avery  method  showed  a  type  4  pneumococcus  (probably 
from  the  mouth).  A  blood  culture  the  following  day  revealed  a  type  1 
pneumococcus. 

In  the  cases,  the  parallelism  between  the  results  of  the  rapid  precipitin 
test  and  the  Avery  method  is  striking.  It  would  seem  to  suggest  that  when 
a  typical  pneumonia  sputum  is  received  on  which  the  rapid  precipitin  test  fails 
to  reveal  a  "type,"  immediate  intraperitoneal  injection  of  a  white  mouse  wiih 
the  washed  sputum  would  be  indicated.  On  the  other  hand,  when  the  rapid 
precipitin  test  is  ])ositive,  it  would  seeiu  justifiable,  so  far  as  we  have  gone, 
to  accept  the  results  for  clinical  purposes,  especially  in  cases  in  which  the 
rapid  precipitin  test  reveals  a  type  1  pneumococcus,  in  whicli  case  immediate 
administration  of  type  1  antiserum  would  be  indicated. 


RANSOHOFF  MEMORIAL  VOLUME 


Two  of  the  patients  in  whom  the  rapid  precipitin  revealed  a  type  1 
pneumococus  were  exceedingly  ill  on  admission  and  in  both  instances  the 
sputum  was  "typed"  witliin  half  an  hour.  In  both  instances  the  ]irompt 
administration  of  type  1  i)neuniococcus  antiserum  was  succeeded  by  re- 
covery. 

Microscopic  examination  of  direct  smears  of  the  sputum  is  of  distinct 
value  in  that  it  gives  an  idea  of  the  relative  numbers  of  pneuniococci  in  the 
sputum.  The  greater  the  number  of  pneumococci  in  a  given  sputum,  if 
they  be  of  one  of  the  first  three  types,  the  greater  will  be  the  amount  of 
pneumococcus  protein  dissolved  by  the  bile  and  the  more  rapid  and  clean- 
cut  will  be  the  precipitin  test  obtained  on  addition  of  the  specific  antiserum. 
Hence  the  sputum  chosen  for  the  test  should  be  that  portion  which  conains 
pneumococci  in  the  largest  numbers,  this  being  usually  the  portion  which  is 
most  streaked  with  blood  or  most  purulent. 


The  method  described  is  a  rapid  precipitin  test  of  filtered  pneumonic 
sputum,  to  which  bile  previously  has  been  added.  By  this  method  a  "typing" 
of  the  pneumococcus  may  be  effected  within  half  an  hour  after  receipt  of 
the  s])utum. 


HYPERPLASTIC  PYLORIC  STENOSIS  OF  IXFANCY* 
DuDi.Kv  W.  r.M.MKu,  M.  I),,  F.  A,  C.  S. 


The  literature  of  congenital  jiyloric  stenosis,  frequently  miscalled  liyi^er- 
trophic,  has  been  so  voluminous  and  tlie  symptomatology  has  been  so  ably 
presented  in  recent  papers  by  Porter,  Holt,  Downes,  Scudder  and  many 
others,  that  it  is  quite  unnecessary  to  review  it  at  this  time.  We  have  all 
heard  of  the  young  man's  prerogative  of  drawing  conclusions  from  a  few 
cases.  I  am  asserting  my  claim  to  this  privilege,  and  with  your  indulgence, 
shall  relate  a  few  experiences  and  draw  a  few  conclusions  from  twenty- 
seven  cases  I  have  observed  of  pyloric  stenosis  in  infants. 

In  the  diagnosis  of  this  condition  the  gastric  wave  is,  I  believe,  the  most 
important  single  symptom  since  it  is  either  jiresent,  or  a  history  of  its  former 
presence  can  be  obtained.  These  waves  may  be  stimulated  by  a  feeding, 
and  when  thus  seen  are  a  definate  evidence  of  pyloric  or  duodenal  obstruc- 
tion. At  the  approach  of  the  terminal  stage  of  emaciation,  the  wave  may 
be  absent,  as  stomach  atony  and  dilation  eliminate  muscular  contraction 
that  is  visible  through  even  the  thin  abdominal  walls  of  the  starved  infaiU. 
All  are  familiar  with  these  waves  that  arise  under  the  left  costal  arch  and 
seem  to  travel  slowly  across  the  epigastrium  to  the  pyloric  area,  diminishing^ 
in  size  and  fading  away  when  this  is  reached.  In  the  more  marked  case, 
during  the  period  of  good  muscular  tone,  there  may  be  a  wave  beginning 
just  as  the  preceeding  one  reaches  the  pylorus.  These  waves  are  as  a  rule, 
accompanied  by  the  usual  evidences  of  abdominal  pain  seen  in  infancy ;  also 
they  are  most  active  just  preceeding  the  characteristic  explosive  vomiting. 
In  all  but  two  cases  in  my  series,  these  waves  have  been  present.  In  one 
case  of  nierycism  or  rumination,  an  operation  was  done  because  of  erroneous 
preoperative  diagnosis.  The  patient  was  a  six  months  old  baby  of  about 
birth  weight.  The  vomiting  was  typical.  The  great  emaciation  led  us  to  be- 
lieve that  gastric  atony  accounted  for  the  absent  waves.  In  the  second  of  these 
two  "waveless"  cases,  the  explanation  of  atony  was  correct.  I  believe  that 
the  greatest  value  of  the  X-ray  in  tliese  cases  is  not  as  an  aid  in  the  making 
of  a  diagnosis,  but  in  the  denionstration  of  the  condition  of  the  muscular 
wall  of  the  stomach,  thus  gi\ing  \isual  data  for  prognosis.  A  stomach  show- 
ing very  weak  or  no  gastric  waves  warrants  the  assumption  of  a  poor  prog- 
nosis and  the  urgent  need  of  emergency  methods.  I  have  seen  cases  in 
which  unquestionably  real  harm  has  been  done  an  infant  because  of  delay, 
due  to  the  report  by  the  roentgenologist  that  the  opaque  meal  had  passed 
on  from  the  stomach  to  the  small  intestines. 

Persistent  gastric  waves  .seen  in  a  vomiting  infant  led  to  only  two  errors 
in  pathologic  diagnosis,  although  the  value  of  this  sympton  in  making  a 
surgical  diagnosis  has  been  100  per  cent.     One  error  occurred  in  an  infant 


RAXSOHOFF  MEMORIAL  VOLUME 


of  eleven  days,  who  had  a  complete  atresia  of  the  duodenum  at  the  junciurc 
of  the  first  and  second  portions,  that  is.  above  the  papilla.  The  child  was 
in  extremis  and  died.  The  second  child  seen  early  this  summer  was  six 
months  old,  its  weight  at  birth  was  8  pounds  1  ounce,  at  operation  8  pounds 
12  ounces.  There  had  been  more  or  less  continuous  or  daily  vomiting  of 
food  and  gastric  secretions,  at  tinies  explosive,  with  very  indistinct  waves 
seen  by  the  last  pediatrician  in  attendance.  The  obstruction  was  only 
relative  as  food  w^as  always  present  in  the  stools,  and  the  weight  fluctuated 
up  and  down  from  birth  weight.  Most  excellent  advice  as  to  feeding  had 
been  given.  No  blood  had  been  vomited,  and  there  w-as  no  history  of  blood 
in  the  stools  though  test  had  not  been  made.  The  preoperative  diagnosis, 
here  too,  was  pyloric  hyperplastic  stenosis  of  a  mild  form.  On  introduction 
of  the  exploring  finger,  I  was  somewhat  chagrined  not  to  feel  an  olive-like 
tumor  at  the  pylorus.  Delivery  of  the  pylorus  showed  a  normally  soft 
unthickened  pylorus  with  a  tag  of  omentum  plastered  to  the  duodenum 
about  1  cm.  distal  to  the  vein.  Other  adhesions  were  present  narrowing  the 
pylorus ;  the  area  under  the  omental  adhesions  was  typically  "stippled"'  and 
scarred.  The  duodenum  was  so  small  that  I  hesitate  to  say  there  was  crater- 
like induration,  ^^'e  were  of  the  opinion  that  the  child  would  not  stand  a 
gastro-jejunostomy,  so  a  pyloropasty  was  made,  cutting  through  the  mucosa 
from  the  duodenum  well  into  the  stomach  and  closing  to  make  the  line  of 
the  wound  at  right  angles.  Bile  was  vomited  once  and  for  four  days  the 
child  did  well  and  gained.  Then  it  began  to  vomit  more  and  more  of  its 
feeding,  until  by  the  tenth  day  it  was  evident  that  further  interference  was 
indicated.  I  almost  hoped  the  family  would  relieve  my  responsibility  i)y 
refusing  a  second  operation,  but  they  did  not,  and  a  posterior  gastrojejun- 
ostomy was  performed.  The  child  gained  rapidly  and  consisteiuly.  douhlint; 
its  weight  in  three  months. 

So  far  as  I  have  investigated  the  rather  scant  literature  of  infantile 
duodenal  ulcer,  I  did  not  find  any  reference  to  operation  in  so  young  an 
infant.  The  gastric  wave  symptom  therefore  is  of  true  surgical  diagnostic 
value. 

I  woidd  like  to  call  attention  to  an  error  almost  univer>ally  made  in 
terminology  by  writers  who  call  this  condition  hpyertrophic.  I  have  had 
but  one  death  due  to  this  congenital  anomaly  and  this  in  an  unoperated 
infant,  but  I  have  seen  material  from  several  cases.  The  histologic  picture 
is  not  hypertrophic  but  hyperplastic.  The  individual  muscle  fibers  are  not 
particularly  increased  in  size,  but  there  are  more  of  them.  Added  to  this  is 
a  varying  amount  of  edema,  and  it  is  this  edema  that  puts  the  finishing 
touch  to  the  picture  in  the  majority  of  the  cases. 

Xo  doubt  there  will  always  be  differences  of  opinion  between  internists 
and  surgeons  as  to  a  certain  group  of  these  cases,  namely,  the  so-called  spasm 
group.  My  own  belief  is  that  there  is  no  such  clinical  entity  as  the"pyloric 
spasm  of  infancy."  and  that  every  case  in  which  the  symptoms  are  inter- 
mittent or  remittent  in  character,  is  at  least  a  mild  case  of  true  hyperplastic 


DUDLEY  W.  PALMER 


pyloric  stenosis.  This  edema  is  a  variable  quantity  producing  by  this  varia- 
tion the  symptoms  of  spasm  the  medical  man  so  delights  to  treat  with  bella- 
donna veratrum-viridi  and  other  drugs.  There  is  just  as  much  reason  to 
say  that  the  enlarged  prostate,  that  in  the  "drunken  spree"  produces  acute 
urinary  retention,  is  due  to  a  spasm.  Similarly  the  obstruction  is  not  a  true 
stenosis  of  the  lumen  of  the  pyloric  canal  any  more  than  of  the  urethra  in 
l)rostatic  hypertrophy.  These  obstructions  are  peri-ureteral  and  peri- 
pyloric. The  above  explanation  is  satisfactory  for  many  of  the  observed 
symptoms  such  as  the  primary  period  of  a  few  days  or  weeks  without  seri- 
ous vomiting.  It  puts  all  these  cases  with  similar  symptoms  into  one  group 
with  a  material  basis  instead  of  forcing  upon  us  the  liecessity  of  evolving 
two  groups  to  explain  an  otherwise  simple  condition. 

I  want  to  call  attention  also  to  the  fact  that  no  reference  was  found  in 
the  literature  to  an  instance  in  which  the  surgeon  opened  up  a  "spasm 
case"  by  mistake  and  found  a  "spasming  pylorus."  On  the  other  hand,  a 
sad  number  of  cases  were  found  in  which  the  infant  had  been  treated  medi- 
cally for  spasms  until  death  from  starvation  occurred  or  the  case  became 
a  grave  surgical  risk.  Surgeons  owe  it  to  these  helpless  children  to  clarify 
the  atmosphere  and  put  this  syndrome  on  a  material  rather  than  an  elusive 
nervous-spasm-theory  basis.  Hutchinson's  statement  that  when  these  in- 
fants get  bad  enough  "they  always  turn  the  corner  and  get  well"  is  not  a 
safe  rule  for  ])rocedure  in  view  of  what  surgery  now  can  offer. 

Before  discussing  the  points  in  the  operation,  I  shall  say  a  few  words 
with  reference  to  the  time  the  operation  is  indicated.  Many  patients  who 
present  rather  acute  symptoms  do  not  need  operation.  Careful  attention  to 
the  feeding,  increasing  the  alkali  intake,  attention  to  the  bowels,  gastric 
lavage,  and  attention  to  air  swallowing  during  nursing  all  are  items  of  well 
known  value  to  the  good  pediatrician.  Watchfulness  in  these  matters  may 
tide  the  infant  over  a  period  when  the  edema  is  symptom-producing. 

Sauer,  in  July,  1918,  was  perhaps  the  first  formally  to  report  the  use  of 
paste  feeding  in  congenital  pyloric  stenosis,  though  I  had  seen  it  used  fre- 
quently before  this  in  some  cases  in  which  I  was  interested.  The  paste  feed- 
ing will  unquestionably  produce  striking  results  in  many  cases,  but  I  do  not 
believe  it  will  prove  a  cure  all.  Porter,  in  discussing  the  matter  at  the 
meeting  of  the  American  Medical  Association,  1919,  said :  "He  may  use  the 
thick  feeding  with  an  assurance  that  a  proportion  of  cases  will  respond  wtih 
complete  restoration  of  digestive  and  nutritional  function,  and  for  stubborn 
ca.ses  there  is  still  left  the  brilliantly  successful  operative  method  of  Fredet, 
which,  used  early  enough,  ougiit  to  obtain  100  per  cent,  of  cures."  This  last 
clause,  in  my  opinion,  rec|uires  and  assumes  a  very  close  co-operation  be- 
tween the  i^ediatrician  and  the  surgeon  to  insure  justice  to  the  child  and  to 
each  other. 

A  period  of  waiting  may  be  desirable  until  iioinial  dilatation  of  the  canal 
occurs  through  physiologic  use  of  the  parts,  and  to  jjcrmit  an  increase  in 
tile  muscular  development  of  the  stomach  to  propel  the  food  along  its  course. 


RANSOM  OFF  MEMORIAL  VOLUME 


While  waiting  it  should  be  remembered  that  a  child  of  two  weeks  weighing 
seven  pounds  is  in  far  better  condition  than  a  child  of  two  months  weighing 
a  pound  or  so  more,  and  the  younger  infant  can  lose  a  pound  with  less  risk. 
A  child  of  about  one  month  even  moderatel)'  well  nourished,  if  it  is  holding 
its  weight,  can  be  treated  paliatively  for  a  couple  of  weeks  while  a  little 
later  a  stationary  weight  may  not  warrant  palliative  treatment.  The  economic 
condition  and  intelligent  co-operation  of  the  mother  also  affect  the  decision 
with  regard  to  treatment.  Needless  to  say  the  child  whose  vomiting  is  ex- 
cessive, whose  stools  are  without  food  content  and  who  is  steadily  and 
rapidly  losing  weight,  is  a  case  for  urgent  surgery.  Other  evidences  point 
to  such  urgency,  such  as  loss  of  skin  elasticity,  sunken  fontanelles.  con- 
centrated or  even  suppressed  urine,  stupor  and  disappearing  displays  of 
hunger.  Finally,  it  may  be  said  that  an  operation  is  safer  than  the  care  of  a 
poor  ])ediatrician.  e\en  though  the  svmptoms  are  mild;  it  is  also  safer  than 
the  average   unintelligent   though   well   meaning  treatment   by   the   i)arents. 


The  Fredet  or  so-called  Ramstedt  operation  has  undoubtedly  lifted  the 
surgery  of  congenital  pyloric  stenosis  from  an  extremely  hazardous  group 
to  the  realm  of  comparatively  safe  surgery.  Operative  risks  and  operative 
mortality  no  longer  incline  one  to  delay ;  on  the  contrary  the  operation  can 
be  advised  to  relieve  the  more  mild  symptoms  and  thus  shorten  and  remove 
the  worry  of  the  parents.  I  have  been  interested  in  watching  several  patients 
for  whom  operation  was  refused,  the  condition  not  being  urgent.  These 
patients  are  still  subject  to  attacks  of  gastric  pain  and  distress  with  eructa- 
tions, and  are  an  untold  worry  to  the  parents.  Undoubtedly,  however,  some 
children  are  left  without  any  symptoms  after  the  original  attack  subsides. 

Practically  every  patient  coming  to  the  surgeon  is  in  a  marked  state  of 
acidosis  and  dehydration.  I  have  adopted  the  principal  thai  a  further  delay 
Pa,jc  .}.;,' 


DUDLEY  IV.  PALMER 


of  twenty-four  hours  in  which  to  prepare  the  infant  is  the  wisest  precedure. 
The  preparation  consists  of  alkahne  gastric  lavage,  alkaline  colon  flushes 
(one  or  two)  ;  enemas  of  from  30  to  75  cc.  every  three  hours  and  from  30  to 
50  cc.  of  normal  salt  solution  subcutaneously  at  three  hour  intervals,  thus 
correcting  a  suppressed  urinary  secretion  and  improving  the  shrunken,  dried 
up  appearance.  The  subcutaneous  injections  may  be  used  after  operation 
for  about  twenty-four  hours  by  which  time  nourishment  is  given  freely. 
Feedings  are  continued  up  to  the  time  of  operation,  in  the  hope  that  some 
part  of  the  retained  food  may  be  passed  on  from  the  stomach  ;  a  thorough 
gastric  lavage  is  given  just  before  operation. 

A  number  of  cases  of  hyperplastic  pyloric  stenosis  is  associated  with 
thymus  enlargement,  producing  very  embarassing  symptoms,  have  occurred 
in  my  practice  and  I  know  of  several  "thymic  deaths"  following  operations 
for  pyloric  stenosis  in  infants.  Two  years  ago  RansohofT  reported  such  a 
case  with  postmortem  finding  in  which  death  occurred  about  seven  months 
after  a  perfect  operative  result.  The  associated  enlarged  thymus  in  my  ex- 
perience has  been  more  frequent  than  the  incidence  of  enlarged  thymus  in 
the  average  infant,  and  the  possibilities  are  so  serious  that  a  routine  x-ray 
picture  should  be  made  of  the  chest  before  operation,  and  followed  by  treat- 
ment if  the  enlargement  is  found.  You  have  all,  no  doubt,  noticed  the  fre- 
quency of  the  references  in  the  literature  to  sudden  deaths  following  opera- 
tion for  pyloric  stenosis. 

It  is  scarcely  necessary  to  call  your  attention  to  the  fact  that  everything 
must  be  done  in  the  operating  room  to  conserve  the  body  warmth  and  to 
expedite  procedures.  Cleansing  the  skin  thoroughly  with  alcohol  is  sufficient. 
The  extremities  must  be  fastened  to  the  table  as  otherwise  their  movements 
on  the  table  may  be  disquieting.  Ether  is  best  for  anesthesia;  very  little 
anesthetic  is  needed  and  a  few  drops  of  ether  make  a  change  from  semi-con- 
sciousness to  a  too-deep  anesthesia,  from  squirming  and  possible  evisceration 
to  suppressed  respiration.  I  have  not  yet  tried  local  anesthesia.  A  high  right 
rectus  incision  extending  well  up  to  the  costal  border,  of  from  2.5  cm.  to 
3.75  cm.  in  length,  is  a  great  advantage,  because  the  normally  low  hanging 
liver  controls  a  tendency  to  evisceration;  later  the  liver  acts  as  a  support 
should  the  integrity  of  the  wound  be  threatened  by  the  secretion  of  serum 
during  the  healing  period.  Two  fingers  are  introduced  and  the  liver 
is  pushed  up.  By  wiggling  the  fingers  very  much  as  Dr.  C.  H.  Mayo  sug- 
gested many  years  ago  for  finding  an  appendix,  an  olive  shaped  mass  is 
palpated.  This  tumor  is  lifted  to  the  surface  and  its  most  avascular  area 
is  incised  longitudinally  down  to  the  mucosa.  Because  the  shape  of  the 
infant's  pyloric  aperature  on  the  duodenal  side  is  very  much  like  the  cervix 
in  a  vagina,  it  is  necessary  to  be  extremely  careful  to  avoid  opening  the 
sulcus  or  gutter  surrounding  the  pylorus.  Such  a  technical  error  adds  greatly 
to  the  risk,  since  a  plastic  operation  or  a  gastrojejunostomy  then  unfortun- 
ately becomes  necessary.  Frequently  one  cannot  avoid  cutting  a  small  vein 
and  as  every  drop  of  blood  counts,  it  has  seemed  wise  to  control  this  with 


RANSOHOFF  MEMORIAL  VOLUME 


a  hot  tal)  of  gauze  applied  directly  to  the  bleeding  point  for  a  few  minutes ; 
this  time  is  well  spent,  I  believe,  as  catgut  ligatures  bite  through  this  edema- 
tous, butter-like  tissue.  The  incision  can  be  extended  well  upon  the  stomach 
side  of  the  pylorus  without  great  risk,  but  it  is  much  safer  to  refrain  from 
attempting  to  cut  the  last  few  muscle  fibers  on  the  duodenal  side.  If  a 
few  fibers  are  left,  spitting  up  or  regurgitation  of  some  food  may  occur;  this 
is  temporary  and  not  alarming  as  the  larger  part  of  the  food  is  retained 
and  the  explosive  vomiting  is  controlled. 

The  pyloric  tumor  is  returned  to  place  without  further  attention  and 
the  liver  dropped  down  behind  the  incision.  A  layer  suture  of  the  abdominal 
wall,  using  a  fine  catgut  (No.  0  chromic  catgut)  with  silk  worm  figure-of- 
eight  fascial  sutures  has  given  the  best  results.  No.  1  or  No.  2  plain  or 
chromic  catgut  is  too  large  to  be  taken  care  of  in  the  abdominal  wall  of  these 
starved  babies.  Even  with  extreme  detailed  attention,  a  rather  large  per- 
centage of  patients  have  a  serum  discharge  that  necessitates  frequent  dress- 
ings for  a  week  or  ten  days.  None  of  the  wounds  in  my  cases  has  had  real 
pus  form  and  none  has  failed  to  heal  tightly  without  hernial  tendencies. 

Patients   with    congenital    hyperplastic    pyloric    stenosis 17 

Patients    operated    upon 23   (85.18%) 

Fredet   operations — 20 

Gastro-enterostomy — 3 
Patients  not  operated  on 4  (14.81%) 

1  died  before  operation   could  be  done. 

2  improved  with  palliative  treatment   (mild   cases). 

1   refused    operation    and    has    occasional    symptoms. 

Males   79% 

First-born  58% 

Average  age  of  patients  at   onset    of    symptoms 14  days 

Average  age  of  patients  when   seen   or   at   operation 02  days 

Average  duration   of  symptoms 48  days 

Thymus  enlargement  proved  to  e.xist  in  patients  operated  on....  26% 

Examination  for  palpable  tumor  positive    37% 

Examination    for   palpable   tumor   doubtful    18% 

E.xamination  for  palpable  tumor  negative   45% 

Waves  visible  95% 

Patients  of  weight  less  than  birth  weight 61% 

BIBLIOGRAPHY 

1.  Dnwne?,  W.  .\.:  Tlie  operative  treatment  of  pyloric  obstruction  in  infants.  Surs.,  Cynec. 
and  Olist,.    1911..   .«ii.  251-257. 

2.  Holt,  L.  K.:  Medical  versus  surgical  treatment  of  pyloric  stenosis  in  infancy.  Joiir.  :\m. 
Med.    .\5sn.,    191-4,   Ixii,   2014-2019. 

3.     Hutchinson,    R.:     Concenital    pyloric   stenosis.      Brit.    Med.    lour..    1910,    ii,    1021-102-t. 

4.  Le\yitt.  VV.  B.,  and  Porter,  L. :  Pyloric  obstruction  in  infants  with  muscular  hypertrophy 
at  the  pylorus.     Jour.  Am.   Med.   .Assn.,   1912,  Ivii,  256-259. 

5.  McClanahan,  H.  M. :  Duodenal  ulcer;  report  of  a  case  in  which  operation  was  followed  by 
improvement.     Jour.  Am.   .Med.    .Assn.,    1916,   Ixvii,    1270-12;i. 

6.  Palmer,   H.    W.:     Hyperplastic   pyloric  stenosis.     .Ann.    Surg.,    1917.    Ixvi.   428-435. 


7.  Porter,   L. :     A   retrospect   of   fifteen  years'   experience   in   the   treatment  of   hypertrophic   ob- 
struction  in  infants.     .Arch.  Ped.,   1919,  x.xxvi,  385-397. 

8.  Ransahoff,    J.    I,.,    and    Woolley.     P.    C:     Operative    cure    of    congenital    pyloric    stenosis. 
Jour.  Am.  Med.  Assn.,   1917,  Ixvii,   1543-1544. 

9.  Sauer,   h.   W.:    The  use  of  thick   farina   in   the   treatment   of   pyloric   stenosis.      Arch.    Ped„ 
1918,  XXXV.   385-400. 

10.      Scuddcr,  C.  L. :     Stenosis  of  the  pylorus  in   infancy.      .\nn.   Surg..    1914,  lix.   239-2.^7. 

Page  m 


COMPLICATIONS  AND  END  RESULTS  OF  BILE  DUCT 
INFECTION.* 

J.  Enw,  riRRrxG.  M.D., 

Cincinnati. 

It  is  generally  ngreed  that  most  of  the  di.seascs  found  within  the  bile 
passages  are  due  to  infection  direct  from  the  duodenum  or  infections  car- 
ried by  the  blood  and  lymph  streams  to  the  liver.  A  considerable  number 
of  these  infections  come  through  the  portal  circulation,  which  is  the  great 
absorptive  and  drainage  system  of  the  intestinal  tract.  A  previous  typhoid 
is  suggestive,  a  long  history  of  constipation,  obstipation,  or  hemorrhoids 
predisposes  to  bile  passage  infections.  Fermentations  and  intoxications  due 
to  an  increased  bacterial  growth  in  the  intestinal  tube  give  an  increased 
work  to  the  liver  cells,  consequently  all  the  bacterial  can  not  be  burnt  up  in 
the  liver ;  some  find  their  way  into  the  bile  passages  and  to  the  gall-bladder. 

Sir  Berkley  Monyhan  has  observed  the  frequent  occurence  of  distentions 
with  in  the  duodenum,  infection  of  its  contents,  duodenum  inflammation, 
duodenal  ulcer  and  gall-stone  in  the  same  patient.  Sir  \\'illiam  Lane  ad- 
vanced a  step  farther.  He  states  that  duodenal  distention  is  the  result  of 
delays  to  the  passage  of  the  fecal  current.  Infections  then  occur  in  the 
intestinal  canal,  inflammation,  ulcer,  and  gall-stones  are  the  result.  Bacteria 
and  their  products  being  absorbed  are  carried  by  the  blood  and  lymph  streams 
to  the  liver,  there  many  of  them  are  destroyed,  others  pass  out  into  the  ducts, 
infecting  the  bile.  The  deposit  of  altered  secretions  of  the  Uver  forms  stone 
in  the  gall-bladder  and  bile  passages.  Infections,  inflammation,  distentions, 
altered  secretions  and  the  consequent  lowered  nutrition,  with  blood  infections 
causes  ulcers  in  the  stomach  and  duodenum.  The  bacteria  usually  found  in 
the  bile  passages  are  bacilli  typhi isus,  bacilli  coli  and  the  pus  producers. 
Persons  leading  a  sedentary  life,  wnnien  past  middle  life,  repeated  pregnan- 
cies, dietary  indiscretions  and  chronic  infections  in  any  of  the  abdominal 
organs  predisposes  to  gall  duct  infections.  The  symptoms  when  stones  are 
present  and  are  passing  through  the  bile  passages  are  well  known  and  need 
no  comment. 

The  History. — The  early  history  is  the  most  important  in  diagnosis  before 
colic  occurs.  Occasionally  hepatic  colic  seems  to  be  the  first  evidence  of 
gall  duct  trouble.  However,  on  close  questioning  in  such  cases,  you  will 
bring  out  the  story  of  a  previous  stomach  trouble,  bilious  spells,  fulness  or 
distention  preceding  the  attack  of  colic.  When  a  patient  comes  to  you  with 
a  history  of  long  and  continued  dyspepsia,  with  nausea,  fulness  in  the 
epigastrium,  rightside  bloating,  constipation  marked,  occasional  bilious  at- 
tacks with  temperature,  severe  pain  in  the  right  side  running  toward  the 
middle  line,  pain  temporarily  relieved  by  vomiting  (vomitus  containing  no 


RANSOHOFF  MEMORIAL  VOLUME 


lilood),  a   presumptive   diagnosis  of   infection   of   tlie   bile   passages  can  be 
made. 

Examination  of  the  stools  during  the  acute  attacks  may  also  help  in  the 
diagnosis.  There  may  be  a  temporary  absence  of  bile  in  the  stool  due  to 
stone  obstruction  or  to  the  congestion  and  swelling  of  the  mucosa  of  the 
ducts.  Gall-stones  are  sometimes  recovered  from  the  stools.  The  above  are 
the  usual  early  symptoms  of  a  persistent  infection  of  the  bile  passages. 
When  physical  signs  occur  you  are  dealing  with  an  end  result  of  infection. 
The  failure  to  elicit  from  the  ])atient  the  symptoms  of  infection  or  stone 
in  the  bile  passages  is  usually  due  to  an  incomplete  questioning.  These  pa- 
tients will  frequently  give  you  the  suggestion  of  gall-bladder  disease  in  their 
history.  You  do  not  require  jaundice,  severe  pain,  a  tumor  mass,  septic 
fever,  itching,  vomiting  and  clay-colored  stools  to  make  the  diagnosis.  These 
are  the  complications  of  infections.  The  time  for  permanent  relief  may  be 
far  past  when  one  or  more  of  these  occur.  They  usually  mean  persistent 
obstructions  of  the  cystic  or  common  ducts  by  stone  or  adhesions ;  peritonitis 
many  times  follows  such  obstructions ;  some  of  the  neglected  cases  of  stone 
are  sure  to  become  cancerous.  An  added  complication  is  that  of  disease  of 
the  pancreas.  If  abscess  of  perforation  occurs  and  the  patient  survives,  the 
adhesions  following  causes  much  distress  from  dypepsia,  and  many  times 
mechanically  obstruct  the  outflow  of  the  bile.  Perforations  from  stones  or 
abscess  may  form  fistulous  tracts  into  the  abdominal  organs  or  lung.  Ex- 
ternal openings  discharging  stones  are  on  record.  Intestinal  obstruction 
from  large  stone  ulcerated  into  the  bowel  are  of  frequent  occurrence. 

The  removal  of  gall-stones  when  they  are  all  still  confined  to  the  gall- 
bladder is  in  the  hands  of  competent  surgeons  now  so  safe  from  an  operative 
standpoint,  and  so  satisfactory  in  the  relief  of  symptoms  when  early  opera- 
tion is  performed,  that  in  all  cases  a  diagnosis  of  infection  or  stones  within 
the  bile  passages  should  mean  early  operation.  If  we  would  only  appreciate 
the  serious  end  results  that  follow  continued  infection,  inflammation,  gall- 
stones, colics,  and  attacks  of  obstructive  jaundice,  there  would  be  less  pepsin 
sold  for  "dyspepsia,"  so-called,  and  fewer  attempts  at  lubrications  and  dis- 
solutions by  the  ingestion  of  "Italian  olive  oils,"  sal  hepatica  and  natural 
waters  (guaranteed  to  dissolve  stone).  Certain  it  is  that  they  will  not  affect 
the  condition.  The  temporary  improvement  sometimes  noted  under  such 
treatment  is  due  to  the  natural  resistance  of  the  tissues. 

The  surgery  of  the  bile  passages  should  not  be  the  surgery  of  the  end 
results  of  infection,  nor  of  the  complications,  rather  we  should  early  attack 
the  infected  gall-bladder  (as  surgeons  now  do  the  appendix),  drain  the 
gall-bladder  early,  relieve  the  infection,  thereby  obviating  the  complications 
which  give  such  unsatisfactory  results.  Medical  eiiforts  at  drainage  through 
the  ducts  usually  fail.  I  would  here  like  to  cite  some  of  my  unsatisfactory 
cases,  unsatisfactory  because  of  delay  in  coming  to  operation.  Surgical 
skill  will  not  and  can  not  recompense  for  delays.    In  the  hands  of  a  coni- 


/.  EDIV.  PIRRUNG 


peteiit  surgeon,  the  early  drainage  cases  should  all  do  well.   The  most  skillful 
surgeon  can  not  relieve  many  of  the  complications  that  arise  from  delay. 

Case  I. — Mrs.  H.,  aged  seventy,  blind  for  thirty  years  (cataracts)  ;  seen 
early  in  the  fall  of  1909;  she  was  having  severe  cramps  in  the  epigastrium. 
She  gave  a  long  history  of  dyspepsia,  eructations,  bloating,  colics  and  con- 
stipation. Her  abdomen  was  tender  to  the  right  of  the  middle  line,  a  tumor 
about  the  size  of  an  egg  was  felt  under  the  edge  of  the  ribs  and  down  deep 
into  the  right  hypochondrium.  There  was  no  jaundice  and  no  enlargement 
of  the  liver.  A  diagnosis  of  cancer  of  the  bile  duct  was  made.  In  October, 
1909,  she  developed  obstructive  symptoms,  jaundice  became  marked  and  the 
liver  greatly  enlarged.  About  the  end  of  October,  1909,  the  post-mortem  was 
made,  there  was  primary  carcinoma  of  the  common  duct.  In  the  center  of  the 
growth  was  a  large  stone  lodged  in  the  duct.  There  were  numerous  smaller 
stones  packed  in  the  liver  ducts  and  in  the  gall-bladder. 

Case  II. — Mrs.  M.,  aged  forty-four,  seen  May,  1909.  She  gave  a  long 
history  of  stomach  trouble  with  repeated  attacks  of  vomiting,  biliousness, 
distention,  colics,  and  during  the  past  year  was  jaundiced  on  several  occa- 
sions. Examination  revealed  tenderness  over  the  liver  and  gall-bladder  re- 
gions. A  tumor  mass  was  felt  near  to  the  head  of  the  pancreas.  A  diagnosis 
of  carcinoma  of  the  bile  ducts  and  head  of  the  pancreas.  No  operation  was 
attempted.  July,  1909,  post-mortem  showed  primary  malignant  disease  in 
the  common  duct  and  at  the  head  of  the  pancreas.  There  were  secondary 
deposits  in  the  liver.    Stones  were  present  in  the  common  duct. 

Case  III. — Mrs.  F.,  aged  twenty,  seen  April  27,  1911.  Three  days  pre- 
vious she  was  taken  with  a  sudden  and  severe  pain  in  the  epigastrium, 
violent  vomiting  ensued,  the  vomitus  containing  bile  and  Ijlood.  Vomiting 
and  pain  were  temporarily  relieved  by  repeated  hypodermics  of  morphia. 
Previously  she  had  three  such  attacks  and  recovered,  except  between  them 
a  fulness  within  the  abdomen  and  stomach  trouble  persisted. 

Examination :  The  upper  adbominal  muscles  were  very  rigid,  the  liver 
dullness  merged  with  a  dullness  of  a  mass  which  extended  downward  and 
inward  towards  the  umbilicus.  Her  temperature  was  100°  F.,  pulse  90 ; 
vomiting  was  again  becoming  a  prominent  feature.  This  was  the  fourth 
day  from  onset.  There  was  no  jaundice.  A  diagnosis  of  perforated  duodenal 
ulcer  or  gall-bladder  was  made  and  patient  sent  to  hospital  for  an  inmiediate 
operation.  At  operation  there  was  found  perforated  and  gangrenous  gall- 
bladder. The  mass  was  omentum  and  pus.  There  were  no  stones.  The 
patient  recovered  after  a  very  long  and  stormy  convalescence.  Her  present 
condition  is  far  from  satisfactory  because  of  adhesions  about  the  pylorus 
and  duodenum. 

Case  I\'. — Geo.  L.,  aged  fifty-six,  first  examination  August,  1906,  diag- 
nosis was  then  made  of  gall-stones.  Operation  was  advised  but  refused. 
Again  seen  during  an  attack  in  December,  1907,  and  in  January,  1908,  also 


RANSOHOFF  MEMORIAL  VOLUME 


September,  1909,  and  September,  1911,  and  again  in  August,  1912.  He  was 
the  son-in-law  of  a  physician.  The  doctor  was  not  convinced  that  he  Iiad 
gall-stones,  hut  rather  believed  he  had  "duodenal  catarrh."  The  present 
attack  of  August,  1912.  was  ushered  in  by  severe  chills,  high  temperature, 
vomiting  and  jaundice.  Diagnosis  by  his  physician  at  this  time  was  malaria. 
His  .symptoms  grew  worse  and  on  the  third  day  an  enormous  mass  was 
found  in  the  right  side.  I  was  then  called  and  diagnosed  obstruction  from 
gall-stones.  He  was  removed  to  the  hospital  and  an  immediate  operation  per- 
formed. The  gall-bladder  contained  one  and  a  half  pint  of  pus  and  bile, 
together  with  hundreds  of  stones.  The  cystic  duct  was  obstructed  by  stone. 
A  further  examination  failed  to  discover  stones  in  the  common  or  liver 
ducts.  Drainage  tubes  were  then  placed  in  the  gall-bladder  and  in  the  fossa 
under  the  gall  bladder.  His  recovery  was  prompt  but  unsatisfactory.  He  has 
liad  no  return  of  colic  or  vomiting,  but  has  a  sense  of  uneasiness  and  stomach 
distress  due  to  pylorus  and  Juodenal  adhesions.  His  gall-bladder  was  drained 
for  a  period  of  six  weeks. 

Case  V. — Miss  M.  D.,  age  thirty-seven,  October.  1911.  Onset  of  present 
illness  was  with  severe  and  sudden  pain  in  the  right  side  accompanied  by 
vomiting,  jaundice,  chills  and  fever.  \\'hen  I  saw  her  she  had  been  ill  for 
five  weeks,  she  had  a  large  and  tender  gall-bladder,  was  deeply  jaundiced; 
she  said  she  had  lost  weight.  Her  past  history  was  that  of  colics  and  dyspep- 
sia, such  attacks  extending  over  a  period  of  thirteen  years.  Operation  re- 
vealed many  stones  packed  into  the  common  duct.  The  gall-bladder  was 
also  filled  with  stones.  The  head  of  the  pancreas  was  enlarged.  Recovery 
from  operation  was  prompt,  all  of  the  symptoms  disappearing,  and  within 
three  or  four  months  she  had  gained  twenty  pounds.  Six  months  later  she 
had  a  recurrence  of  jaundice,  chills,  fever  and  vomiting.  The  jaundice  was 
persistent.  Being  unable  to  determine  whether  stone  or  malignancy  existed, 
I  again  explored  the  regions  of  the  pancreas  and  gall-bladder.  The  head 
of  the  pancreas  was  much  enlarged  and  obstructing  the  common  duct.  No 
stones  were  present.  Malignancy  was  now  certain.  Nothing  could  be  done. 
The  patient  failed  to  recover  from  the  second  operation,  died  on  the  tliird 
day  following. 

Case  \'l. — Mrs.  L.,  aged  forty-two.  She  had  had  years  of  stomach  dis- 
tress, gall-stones,  colic  and  dyspepsia.  For  the  past  eight  years  she  had  taken 
morphia  for  the  relief  of  pain.  In  January,  1913,  she  decided  that  she  would 
be  operated  upon.  Examination  showed  an  enlarged  and  tender  gall-bladder, 
the  tenderness  extending  toward  the  mid-line  and  into  the  region  of  the 
pylorus.  Exploration  was  done  under  intravenous  hedonal  anesthesia. 
Malignancy  of  the  duct  was  certain.  No  attempt  was  made  to  remove  stones 
that  were  present.  She  is  still  alive;  there  is  at  the  present  lime  an  extension 
of  the  growth  into  the  li\er.  Three  to  five  grains  of  morphia  are  required 
daily   for  licr  relief.    Her  existence  is  miserable. 


/.  EDIV.  PIRRUNG 


T  could  add  other  cases  to  the  above  list,  but  the  few  herein  reported 
will  sutTice  to  make  my  point,  that  stasis  of  the  bile  within  the  bile  pas- 
sages, infections,  gall-stones  and  chronic  pancreatitis  are  the  forerunners 
of  cancers  of  the  organs.  When  cancer  does  not  develop  chronic  invalidism 
or  morphinism  many  times  occur.  Abscess  and  perforation  are  other  of 
the  complications.  Diabetes  of  hepatic  origin  or,  rather,  diabetes  following 
infections  in  the  liver  and  ducts  is  not  so  uncommon.  I  have  observed  two 
cases  of  diabetes  developing  after  gall-stones,  in  women  who  previously 
had  had  no  sugar  in  their  urine.  Both  of  these  cases  refused  operation.  The 
infection  in  these  two  cases  was  of  long  standing.  Five  or  six  years  of  re- 
curring infection,  jaundice  and  colics. 

These  cases  were  taken  from  a  series  of  operations  upon  the  gall-bladder 
and  bile  ducts  done  within  the  past  five  yeafs.  In  Cases  I  and  II  of  this 
report  no  operation  was  attempted.  The  cases  were  evident  cancer  at  the 
time  of  my  first  examination.  Case  III  shows  the  evil  result  of  persistent 
infection  causing  perforation  of  the  gall-bladder.  There  were  no  stones  in 
this  case,  obstruction  was  caused  by  adhesions.  Bacterial  invasion  of  the 
mucosa  and  submocasa  caused  obstruction  and  perforation.  The  blood 
vomited  in  Case  III  may  have  come  from  a  duodenal  ulcer,  mucous  erosion 
occurring  because  of  the  infected  bile  flowing  into  the  duodenum.  Cases  I, 
II,  V  and  VI  were  cases  of  cancer  developing  from  the  chronic  irritation 
of  stone  lodged  in  the  ducts.  In  the  cases  operated.  Case  \  had  a  history 
of  gall-bladder  infection  and  stone  extending  over  a  period  of  nearly  thir- 
teen years.  Case  VI  had  taken  morphine  for  the  relief  of  gall-stone  colic 
for  eight  years.  Such  conditions  should  not  be  allowed  to  persist.  Patients 
should  be  advised  of  the  complications  likely  to  arise.  Operations  performed 
early  will  obviate  such  complications,  and  it  is  the  duty  of  the  physician 
to  warn  the  patient  of  the  danger. 

At  the  close  of  a  clinical  lecture  delivered  at  the  Infirmary,  New  Castle- 
on-Tyne  (British  Medical  Journal,  January  3,  1914),  Mr.  Rutherford  Mor- 
rison said :  "Lives  are  still  lost  that  could  be  saved  and  a  delay  not  so  dan- 
gerous often  means  prolonged  convalescence  and  a  dangerous  illness  which 
might  have  been  averted  by  more  accurate  diagnosis  and  more  prompt  ac- 
tion. Improvement  has  been  most  marked  in  the  more  tragic  conditions, 
such  as  some  perforating  gastric  and  duodenal  ulcers,  because  symptoms 
are  so  serious  and  so  pronounced  that  everyone  concerned  is  convinced  that 
something  should  be  done  without  unnecessary  delay.  There  are  still  too 
many  appendix  cases  left  to  form  abscess  or  to  develop  peritonitis  before 
operation,  and  still  more  gall-stones  left  till  serious  complications  such  as 
abscess,  common  duct  obstruction  and  cancer  render  operations  serious  and 
unsatisfactory." 

My  plea  then  is  to  drain  the  gall-bladder  early  in  infections.  When  gall- 
stone colic  occurs  there  can  be  no  permanent  relief  except  that  offered  by 
operation.  If  ulcer  of  the  duodenum  is,  as  Monyhan  and  others  believe  it 
to  be,  due  to  infection,  is  it  not  reasonable  to  suppose  that  an  infected  bile 


RANSOHOFF  MEMORIAL  VOLUME 


continually  pouring  into  the  intestinal  tract  would  add  to  the  chances  of 
ulcer  in  the  duodenum?  Cancer  arising  from  chronic  irritation  is  admitted 
by  many  observers.  A  stone  lodged  in  the  gall-bladder  or  ducts — more  par- 
ticularly the  ducts — is  potentially  a  cause  of  cancer  of  those  organs.  Diabetes 
of  hepatic  organs,  pancreatitis  and  some  of  the  abscesses  of  the  j)ancreas 
can  lie  prevented  by  the  early  drainage  of  an  infected  bile. 


rHE   INFLUENCE  OF   BILE  ON  THE   FAT-SPLITTING 
PROPERTIES   OF  PANCREATIC  JUICE.* 

By  B.  K.  Raciiford.  M.  D. 


Plate  I. 

In  the  sjiring  and  sinner  of  last  year,  in  the  Berlin  Physiological  Lab- 
oratory, I  made  a  stndy  of  the  fat-splitting  properties  of  pancreatic  juice 
and  read  a  paper  on  this  subject  before  the  physiological  section  of  the 
Tenth  International  Medical  Congress.  The  complete  and  more  detailed 
])resentation  of  this  work  is  the  object  of  this  paper. 

The  short  pai)er  on  emulsion,  apart  from  any  interest  or  value  that  may 
attach  to  this  portion  of  the  paper  itself,  is  of  importance  because  of  its 
bearing  on  the  methods  used  in  the  study  of  pancreatic  juice. 

I'.MULSIONS 

In  1870  E.  V.  l!rucke'  announced  the  fact  that  when  rancid  oil-  is  shaken 
with  a  solution  of  sodium  carbonate  and  certain  other  alkaline  fluids  an 
immediate  emulsion  results.  He  believed  that  the  oil  was  broken  into  fine 
globules  by  the  shaking  and  that  the  soap  formed  served  to  hold  the  eiuulsion 
by  preventing  the  union  of  the  oil  globules. 

In  1878  Johannes  Gad-*  called  attention  to  the  fact  that  when  oil  contain- 
ing the  i)roper  percentage  of  fatty  acid  was  placed  on  the  surface  of  a  car- 
bonate of  sodium  solution  a  beautiful  spontaneous  emulsion  resulted,  and 
from  this  he  held  that  neither  shaking  nor  any  other  outside  mechanical  force 
was  necessary  to  the  formation  of  an  emulsion,  but  that  the  chemical  force 
developed  by  the  soap  formation  was  of  itself  sufficient  under  favorable 
circumstances  to  break  the  oil  drops  into  the  finest  emulsion  globules.  There 
is  but  little  room  for  doubt,  I  think,  that  Gad  is  right  in  his  opinion.  In  fact, 
the  only  question  which  might  arise  is  whether  the  force  developed  by  the 
soap  formation  is  not  a  physical  (Quincke)  rather  than  a  chemical  one.  Gad 
also  believed  with  Brucke  that  the  soap  formed  had  much  to  do  with  holding 
the  emulsion,  and  this  proposition  is,  I  think,  now  everywhere  accepted, 
although  opinions  dififer  widely  as  to  the  manner  in  which  the  soap  acts  in 
bringing  about  this  result. 

I  wish  here  to  call  attention  to  the  method  used  by  Gad  in  his  study  of 
spontaneous  emulsion,  since  this  method  is  the  basis  of  the  methods  used  by 
me  in  the  study  of  the  fat-splitting  properties  of  pancreatic  juice. 

A  54  %  carbonate  of  sodium  solution  is  placed  in  a  series  of  watch- 
glasses,  and  drops  of  oil  containing  different  percentages  of  fatty  acid  are 
gently  placed,  by  means  of  a  pipette,  on  the  surface  of  the  fluid  in  the  watch- 

^S,u'"l,KsL.idirVkr°  WMe'ner"  Aca'd.  Xr'''VV'i5s*lns^^^        lid.    Ixi,    ii,    Aliih.,    i,.    ii.J. 
■'  V.y  raiiciii  ..il  is  meant  oil  containing  fatty  acid. 
Aicl.iv.   fill    .\iiat.  u.  Physiol.,   1878,  p.   181. 


RANSOHOn-  MEMORIAL  VOLUME 


glasses.  The  amount  of  spontaneous  emulsion  in  the  various  glasses  is  care- 
fully noted  and  compared,  and  in  this  way  one  can  readily  ascertain  the 
percentage  of  fatty  acid  required  to  give  the  best  emulsion. 

It  must,  of  course,  be  remembered  in  this  connection,  that  the  percentage 
of  fatty  acid  required  to  give  the  maximum  amount  of  spontaneous  emulsion 
will  \ary  with  other  conditions:  such  as  temperature,  strength  of  soda  solu- 
tion, etc..  and  that  therefore  only  experiments  made  under  similar  conditions 
can  he  compared.  By  this  method  Gad  observed  that  under  otherwise  similar 
conditions  a  certain  definite  percentage  of  fatty  acid  must  be  present  in  oil 
to  give  the  maximum  amount  of  spontaneous  emulsion.  For  example,  he 
found  that  with  a  ^  %  carbonate  of  sodium  solution  at  room  temperature, 
aboitt  5J.2  %  of  fatty  acid  was  required,  and  that  with  increasing  or  diminish- 
ing per  cents,  of  acid  above  or  below  5^^  per  cent,  he  got  less  and  less  emul- 
sion, until  finally  there  was  no  emulsion  at  all.  A  \ery  little  more  or  less 
than  5y2  per  cent,  of  acid  gave  an  incomplete  emulsion.  He  found,  therefore, 
that  ihe  limits  of  good  spontaneous  emulsibility  were  not  only  constant  but 
also  quite  narrow,  and  upon  the^e  important  facts  depends  the  value  of 
his  method. 

W'e  have  in  Gad's  method  a  simple  and  accurate  means  of  determining 
the  proper  percentage  of  fatty  acids  for  giving  the  best  spontaneous  emul- 
sion of  any  given  oil  under  given  conditions. 

After  repeating  the  experiments  of  Gad  and  contirming  his  observations 
I  devoted  considerable  time  to  the  study  of  the  influence  of  shaking  and 
other  outside  mechanical  means  on  the  formation  of  emulsions. 

The  oil  used  almost  exclusively  in  my  experiments  was  olive  oil  that 
had  been  neutralized  by  shaking  for  two  hours  with  a  saturated  solution 
of  barium  hydrate  at  a  temperature  of  95°  C.  and  then  pipetted  and  filtered. 
Oil  freshly  prepared  in  this  manner  w-ill  be  found  practically  neutral,  and 
the  term  neutral  olive  oil  as  used  in  this  paper  always  refers  to  such  oil. 

The  stirring  was  done  chiefly  by  currents  of  air  carried  from  a  blowing 
machine,  into  the  liquids  to  be  stirred  h\  means  of  rubber  tubing  and  glass 
rods.  This  method  is  not  only  more  convenient  but  it  has  other  advantages 
o\er  the  ordinary  one  of  shaking  the  tube. 

My  exj^eriments   led  me  to  the   following  conclu>ions : — 

1st.  Xo  amount  of  stirring  will  give  a  permanent  emulsion  of  either 
neutral  olive  oil  or  (if  rancid  olive  oil  in  distilled  water.  (  P"rey^  found  dif- 
ferently.) 

2nd.  Xo  amount  of  stirring  will  give  a  permanent  enmlsion  with  neu- 
tral olive  oil  and  a  Y^  %   carbonate  of  sodium  solution. 

3d.  Shaking  rancid  oil  and  a  %  %  carbonate  of  sodium  solution  gives 
a  good  permanent  emulsion,  even  though  the  oil  contain  a  very  small  or 
a  very  large  percentage  of  fatty  acid. 

From  the  above  observations  we  >ee  that  when  the  conditions  for  soaj) 
formation  are  present,  shaking  very  nuicli  widens  ihe  range  of  good  cmul- 

'Arcliiv,    fill    Anat.    u.    Physiol.,    IHl.   ]).    .!,'<-'. 
Pai/c   J,ti2 


B.  K.  RACHFORD 


sibility  and  promotes  the  formation  of  a  good  permanent  emulsion,  but 
when  the  conditions  for  soap  formation  are  not  present,  the  shaking  has  no 
influence  whatever. 

In  our  study  of  emulsions  we  must  remember  that  two  things  are  nec- 
essary to  the  formation  of  a  good  permanent  emulsion. 

1st.     The  oil  must  be  broken  into  very  fine  globules. 

2nd.  These  globules  must  not  only  be  prevented  from  running  together, 
but  they  must  also  remain  rather  uniformly  distributed  throughout  the 
liquid.  Now  since  we  know  that  soap  and  certain  other  materials,  as  albumen 
and  mucilage,  have  the  power  of  holding  emulsions,  it  would  seem  an  easy 
matter  to  make  a  mechanical  emulsion  by  shaking  neutral  oil  in  a  solution 
of  soap,  albumen  or  mucilage  ;  but  such  in  truth  is  not  the  case.  In  my 
experiments  with  soap  solution  and  neutral  olive  oil  I  found  that  in  very 
heavy  solutions  of  soap,  by  violent  and  prolonged  stirring,  I  could  get  only 
an  imperfect  emulsion,  one  in  which  the  oil  globules  were  larger  and  more 
variable  in  size  than  those  formed  by  spontaneous  emulsion. 

These  mechanical  emulsions  do  not  approach  in  perfection  a  physiological 
emulsion,  such  as  milk ;  and  they  can  be  formed  only  in  very  viscous  liquids 
and  with  such  great  mechanical  force  as  to  place  them  beyond  the  pale  of 
physiological  importance. 

For  the  study,  therefore,  of  the  influence  of  stirring  in  the  formation  of 
good  permanent  emulsions,  such  as  may  have  some  physiological  importance, 
we  must  return  to  the  experiments  already  noted,  where  a  moderate  amount 
of  stirring  very  much  hastened  and  promoted  the  formation  of  good  emul- 
sions when  the  conditions  for  soap  formation  were  present. 

The  influence  of  stirring  under  such  circumstances  may,  I  tiiink,  be  ex- 
plained as  follows.  When  too  little  acid  is  present  for  the  formation  of  a 
good  spontaneous  emulsion,  the  shaking  or  stirring  simply  favours  the  emul- 
sion by  promoting  soap  formation.  It  breaks  the  oil  into  a  number  of  small 
globules  which  are  constantly  presenting  new  surfaces  to  the  surrounding 
alkaline  fluid,  thus  enabling  the  soda  to  combine  with  all  the  fatty  acid  pres- 
ent, in  the  formation  of  soap,  and  the  chemical  force  thus  liberated  by  the 
soap  formation  becomes  an  important  factor  in  the  breaking  of  the  oil  dro]5s 
into  the  fine  emulsion  globubes,  just  as  it  does  in  pure  spontaneous  emulsion. 

When  too  much  acid  is  present  for  good  spontaneous  emulsion,  the  pro- 
cess is  brought  to  a  stand-still  by  the  formation  of  a  heavy  soap  membrane 
between  the  oil  drop  and  the  alkaline  fluid,  thus  preventing  further  soap 
formation.  Under  these  conditions,  shaking  breaks  the  oil  drop  and  con- 
sequently the  soap  membrane,  thus  constantly  presenting  new  surfaces  of 
oil  to  the  surrounding  alkaline  fluid  and  in  that  way  favouring  soap  for- 
mation and  the  resulting  emulsification.  We  see,  therefore,  that  while  shak- 
ing may  play  a  very  important  role  in  the  formation  of  emulsions,  its  action 
is  chiefly  an  indirect  one,  promoting  emulsification  by  favouring  soap  forma- 
tion, and  that  the  chemical  force  liberated  by  this  jirocess  's  the  force  most 
acti\e  in  breaking  the  oil  dro])s  into  fine  emulsion  glolniles.    From  my  experi- 


RANSOHOFF  MEMORIAL  VOLUME 


ments  I  formulate  tlie  following  general  law  concerning  the  influence  of 
stirring  in  the  formation  of  emulsions. 

The  amount  of  stirring  required  to  give  a  good  emulsion  of  oil  in  a  34  % 
carbonate  of  sodium  solution  will  be  in  inverse  proportion  to  the  nearness 
with  which  the  percentage  of  fatty  acid  in  the  oil  approaches  the  proper 
percentage  for  giving  the  maximum  amount  of  spontaneous  emulsion.  If  the 
oil  contains  the  exact  percentage  of  fatty  acid  for  giving  the  best  s]5ontaneous 
emulsion,  then  the  shaking  will  be  superfluous,  since  a  good  emulsion  will 
form  without  motion  and  no  amount  of  shaking  can  improve  it.  If,  on  the 
other  hand,  the  oil  be  entirely  free  from  fatty  acid,  then,  as  we  have  seen, 
no  amount  of  shaking  will  give  a  good  emulsion.  Between  these  two  ex- 
tremes the  above  law  applies,  and  shaking  may  contribute  very  largely  to 
the  formation  of  emulsions. 

In  the  application  of  the  above  principles  we  have  a  simple  and  convenient 
method  of  determining  when  an  oil  is  practically  free  from  fatty  acid ;  viz., 
shake  it  with  a  J4  %  solution  of  carbonate  of  sodium,  and  if  there  be  no 
fatty  acid  present,  the  mixture  rapidly  clears. 

By  the  same  method  we  may  tell  when  we  ha\e  fatty  acid  free  from 
admixture  with  oil ;  viz.,  shake  the  fatty  acid  with  the  soda  solution,  and 
if  oil  be  present  we  will  have  more  or  less  milky  whiteness,  which  is  char- 
acteristic of  emulsions;  but  if  no  oil  be  present,  we  will  have  a  simple 
cloudiness  due  to  the  insoluble  soap  formed.  From  all  that  has  been  said, 
it  follows  as  a  logical  conclusion  that  the  energy  required  to  make  an  oil 
enuilsible  will  be  in  direct  proportion  to  the  stability  of  the  oil  molecule  of 
the  given  oil.  The  more  stable  the  oil  molecule,  the  more  energy  required 
to  split  it  into  fatty  acid  and  glycerine.  It  matters  not  whether  the  energy 
be  in  the  form  of  heat  or  of  organized  ferments,  bacteria,  or  of  unorganized 
ferments  as  the  fat-splitting  ferment  of  the  pancreas. 

During  my  experiments  I  found  that  heating  neutral  olive  oil  develoiied 
fatty  acid  and  made  it  emulsible,  and  that  if  this  heated  oil  be  again  neutral- 
ized it  became  non-emulsible,  thus  showing  the  emulsibility  to  be  due  to  the 
acidity.  I  also  found  that  the  greater  the  heat  and  the  longer  applied,  the 
more  fatty  acid  was  developed,  so  that  boiled  olive  oil  contained  too  much 
acid  for  good  spontaneous  emulsibility. 

It  is  an  interesting  fact  that  the  acids  freed  by  healing  various  oils 
seemed  to  have  greater  power  in  making  them  emulsible  than  a  like  quantity 
of  oleic  acid.  This  is  especially  true  of  castor  oil.  Castor  oil  is  not  made 
more  emulsible  by  the  addition  of  oleic  acid,  but  after  boiling,  it  may  be 
emulsified  by  shaking  it  with  sodium  solution,  but  it  never  becomes  spon- 
taneously emulsible;  this  latter  fact  Gad  called  attention  to  and  thought 
it  due  to  the  viscosity  of  this  oil.  The  stability  of  the  castor  oil  molecule  is 
shown  by  the  great  heat  required  to  devclo])  sufficient  fatty  acid  to  give  an 
emulsion.  These  facts  seem  to  indicate  that  the  fatty  acids  of  an  oil  are 
the   fatty  acids   best   adapted    for  giving  emulsibility   to  this   particular  oil. 

Page  .iU.'i 


B.  K.  RACHFORD 


It  is  a  physiological  fact  beyond  dispute  that  the  splitting  of  fats  is  a 
most  important  preliminary  step  in  fat  digestion.  That  the  cooking  of  fats 
will  develop  in  them  fatty  acid  is  therefore  a  fact  of  considerable  physio- 
logical importance  and  one  that,  so  far  as  I  know,  has  not  previously  been 
noticed. 

As  I  have  previously  intimated,  it  is  my  belief  that  the  chemical  force 
developed  by  soap  formation  is  the  chief  factor  in  the  formation  of  all 
physiological  emulsions,  that  it  plays  quite  as  important  a  role  in  the  forma- 
tion of  the  emulsion  as  the  soap  does  in  holding  it  after  it  is  formed. 

That  soap  has  the  property  of  holding  emulsions  is,  I  think,  an  undis- 
puted fact,  but  the  manner  in  which  the  soap  acts  is  a  question  concerning 
which  there  has  been  much  difference  of  opinion.  In  explanation  of  this 
difficult  ijrobleni  I  wish  modestly  to  express  my  belief  in  a  theory  of  emul- 
sions which  is  a  modification  of  that  offered  by  Gad.  Gad  believed  that  the 
fine  globules  of  oil  were  coated  as  soon  as  formed,  with  insoluble  soap 
particles  which  formed  a  protecting  envelope  that  prevented  the  oil  drops 
from  running  together.  The  modification  which  I  offer  is  as  follows:  the 
chemical  jMOcess  of  soap  formation  which  breaks  the  oil  into  fine  globules 
nuist  develop  considerable  heat,  this  must  necessarily  have  the  eft'ect  of 
bringing  a  certain  amount  of  otherwise  insoluble  soap  into  solution.  This 
heat  will  necessarily  be  local  and  felt  chiefly  just  at  the  point  where  the  soap 
is  formed,  and  all  the  surrounding  liquid  will  be  cooler.  The  soap  therefore 
which  is  brought  into  solution  by  the  heat  either  is  precipitated  a  moment 
later  en  coming  in  contact  with  coi>ler  parts  of  the  liquid,  or  it  causes  in- 
creased viscosity  in  the  liquid. 

We  may,  therefore,  say  that  the  heat  is  developed,  the  soap  formed  and 
dissolved  and  the  oil  broken  by  the  same  force  in  the  same  place  and  at  the 
same  time.  By  this  mechanism  the  oil  globules  are,  as  soon  as  formed,  coated 
with  a  liquid  soap  which  a  moment  later  hardens  about  them  in  the  form 
of  soap  membranes.  These  soap  membranes  at  the  moment  of  their  forma- 
tion are  not  as  capable  of  holding  the  globules  as  they  are  later,  when,  on 
cooling,  they  become  more  resisting.  If  this  theory  be  true,  it  would  follow 
that  an  appreciable  length  of  time  must  elapse  after  the  formation  of  an 
emulsion  before  it  reaches  its  highest  degree  of  stability.  And  this  in  fact 
I  find  to  be  true,  that  the  emulsions  can  be  more  easily  destroyed  at  the 
moment  of  their  formation  than  later,  and  it  is  only  in  explanation  of  this 
and  other  facts  that  the  above  theory  is  offered.  The  following  conclu- 
sions I  draw  from  my  experiments,  and  some  of  them  are  best  explained 
by  this  theory. 

1st.  If  bile  be  present  an  emulsion  cannot  form,  although  all  the  con- 
ditions otherwise  favourable  to  its  formation  be  present.  This  fact  was 
pointed  out  by  Gad,  and  he  offered  in  explanation  that  the  soap-dissolving 
properties  of  the  bile  prevented  the  formation  of  insoluble  soap  membranes, 
and  that  the  unprotected  oil  globules  ran  together  and  came  to  the  surface 
as  free  oil. 


RAXSOHOFF  MFMORIAL  VOLUME 


2nd.  If  bile  is  added  to  an  emulsion,  the  moment  after  it  is  formed 
the  emulsion  rapidly  clears  by  creaining,  but  no  free  oil  appears  on  the  sur- 
face. Here  it  seems  that  the  soap  not  in  membranes  is  dissolved.  This 
increases  the  specific  gravity  and  diminishes  the  vicosity  of  the  liquid,  and  as 
a  result  the  soap-coated  globules  rise  to  the  surface  as  cream;  why  it  is 
that  the  soaj)  in  the  membranes  more  quickly  acquires  the  property  of  re- 
sisting the  solvent  action  of  bile  than  the  soap  not  in  membranes  I  cannot 
say.  yet  this  seems  the  only  explanation  of  the  above  phenomenon. 

3rd.  If  bile  be  added  to  an  emulsion  some  minutes  after  it  has  formed, 
it  has  no  efTect  in  destroying  the  emulsion.  The  above  propositions  clearly 
indicate  that  an  appreciable  length  of  time  must  elapse  after  the  formation 
of  an  emulsion  before  it  reaches  its  highest  degree  of  stability. 

4th.  One-tenth  per  cent,  nitric  and  sulphuric  acid  and  one-fifth  per 
cent,  lactic  acid  solutions  rapidly  destroy  emulsions,  the  free  oil  running 
to  the  surface.  Acids  destroy  emulsions  by  combining  with  the  base  of 
soaps  and  freeing  the  fatty  acids ;  the  soap  being  thus  destroyed,  the  liquid 
is  much  less  viscous  while  the  specific  gravity  is  very  little  altered.  The  oil 
globules  are  therefore  driven  to  the  surface  as  cream,  but  if  the  acid  be 
stronger,  the  soap  in  membrane  is  also  destroyed,  and  free  oil  floats  on  the 
surface.  The  membrane  soap  is  here  found  to  be  more  resisting  to  soap 
destroyers  than  soap  not  in  membranes. 

5th.  Hydrochloric  acid  has  a  much  less  destructi\e  influence  on  emul- 
sions than  has  nitric  or  sulphric  acid,  and  lactic  acid  has  a  less  destructive 
influence  than  acetic. 

6th.  If  sapo  niedicatus^  be  shaken  in  a  Vv>%  nitric  or  sulphuric  acid 
solution  the  soda  of  the  soap  will  combine  with  the  nitric  or  sulphuric  acid 
and  fine  globules  of  free  fatty  acid  will  rise  to  the  surface.  Sapo  medicatus 
is  more  easily  destroyed  by  nitric  and  sulphuric  acids  than  it  is  by  hydro- 
chloric acid.  These  facts  strongly  corroborate  the  opinion  that  acids  destroy 
emulsions  by  destroying  soaps. 

THE  FAT-SPLITTING  PROPERTIES  OF  PANCREATIC  JUICE 
Since  the  publication"  of  Claude  Bernard,  physiologists  have  generally 
believed  that  pancreatic  juice  has  the  property  of  splitting  neutral  fats  into 
fatty  acids  and  glycerine.  Claude  Bernard  himself  believed  that  the  pan- 
creatic juice  had  a  two-fold  action  on  fats.  In  the  first  place,  he  said  that 
when  neutral  oil  and  pancreatic  juice  were  shaken  together  an  instanfaeous 
emulsion  resulted.  In  the  second  place,  that  the  prolonged  action  of  pan- 
creatic juice  on  neutral  oil  would  develop  fatty  acid.  He  did  not  in  any 
way  associate  these  two  processes  and  believed  them  to  be  due  to  entirely 
different  properties  of  the  juice,  the  emulsion  being  an  instantaneous  process 
and  the  fat  splitting  occurring  only  after  considerable  time.  .\nd  these  two 
processes  are  still  described  as  separate  and  distinct  properties  of  pancreatic 

"A  soda  soap  made  with  olive  oil  acids. 


B.  K.  KACHFORD 


juice  in  some  of  our  most  recent  text-books.  But  since  the  publications  of 
Ilrucke  and  Gad.  most  German  physiologists  have  associated  these  pro- 
cesses, believing  that  the  emulsion  was  wholly  due  to  the  fatty  acid  which 
had  been  developed  in  the  oil  by  the  fat-splitting  ferment  and  that  the 
matter  of  inference  from  the  works  of  Brucke,  Gad  and  others,  rather  than 
from  actual  experiments  with  the  juice  itself.  I  have  failed  to  find  that  any 
systematic  work  in  this  direction  had  been  done  with  pancreatic  juice  since 
the  days  of  Claude  Bernard.  Quite  a  number  of  attempts  have  been  made, 
but  the  difficulties  in  obtaining  a  normal  juice  were  so  great  that  no  exten- 
sive work  has  been  done  and  no  important  fact  added  to  our  knowledge. 
But  while  almost  no  work  has  been  done  with  the  juice  itself,  an  immense 
amount  of  work  has  been  done  with  pancreatic  extracts  and  infusions  made 
from  the  gland.  Physiologists  have  seemed  to  take  for  granted  that,  in 
studying  the  physiological  properties  of  pancreatic  juice,  the  juice  itself 
offered  no  advantage  over  these  extracts.  In  fact  they  seemed  to  believe 
from  the  great  difficulty  in  obtaining  a  normal  juice  that  the  extracts  were 
preferable,  and  our  knowledge  of  the  present  day  is  based  almost  exclusively 
on  experiments  with  the  extracts,  and  but  for  the  fact  that  they  contain  a 
fat-splitting  ferment  the  time-honoured  opinion  of  Claude  Bernard  would 
have  carried  but  little  weight.  For  these  reasons,  a  systematic  investigation 
into  the  fat-splitting  properties  of  the  pancreatic  juice  seemed  to  oiifer  a 
fertile  field  for  work. 

Although  in  the  beginning  tlie  obstacle  of  obtaining  normal  juice  in 
sufficient  C|uantities  to  prosecute  this  investigation  seemed  insurmountable, 
yet  I  was  fortunate  enough  to  hit  upon  a  method  by  which  I  could  readily 
obtain  from  the  rabbit  a  normal  juice  in  sufficient  quantities  for  experimental 
purposes.  The  operation  for  temporary  pancreatic  fistula  in  the  rabbit  is 
easily  and  quickly  done  as  follows:  Make  an  abdominal  incision  in  the 
linea  alba  two  and  one  half  inches  long.  Bring  the  duodenum,  which  is 
readily  found  high  up  in  the  right  hypochondriac  region,  through  this  open- 
ing, run  down  the  gut  to  a  point  where  the  peritoneum  binds  it  so  closely  that 
it  will  not  come  through  the  opening,  and  just  at  this  point  will  be  found 
the  pancreatic  duct  as  it  runs  through  a  leaf  of  the  pancreas  to  the  small 
intestine.  Resect  two  inches  of  the  intestine  at  this  point,  leaving  its  mesen- 
teric attachment,  tie  the  cut  ends  of  the  intestine  above  and  below  and  drop 
them  in  the  cavity,  bringing  the  resected  portion  through  the  adbominal 
wound.  The  abdominal  wound  is  now  partially  closed  by  stitches,  leaving 
only  sufficient  opening  for  the  mesentery  running  to  the  resected  gut.  This 
resected  gut  is  now  laid  open  opposite  the  mesenteric  attachment  and  spread 
out  on  the  abdominal  wall.  The  ends  of  the  gut  are  clamped  and  its  margins 
])acked  with  absorbent  cotton  to  prevent  bleeding.  Insert  a  small  glass  can- 
ula  through  the  pancreatic  papilla  into  the  pancreatic  duct  and  cover  the 
exi)osed  mucous  membrane  with  absorbent  cotton  saturated  with  common 
salt  solution.  The  flow  of  juice  begins  at  once  and  continues  from  four  to 
six  hours.    In  this  manner  about   1   cc.  of  juice  uniform  and  powerful  in 


RAXSOHOFF  MEMORIAL  VOLUME 


physiological  action  may  be  collected.  This  operation  is  a  modification  of 
the  Heindenhain  permanent  fistula  operation"  and  has  the  advantage  of 
being  simple  and  uniformly  successful. 

In  my  experiments  I  used  the  pancreatic  juice  of  the  rabbit,  as  it  seemed 
quite  impossible  for  me  to  obtain  from  the  dog  a  normal  juice  in  sufficient 
quantities  for  experimentation.   The  fat  used  was  neutral  olive  oil. 

I  worked  for  several  weeks  with  very  faulty  methods  before  I  hit  upon 
the  method  which  I  afterwards  used  and  which.  I  think,  is  admirably 
adapted  to  the  study  of  the  fat-splitting  properties  of  pancreatic  juice.  The 
foundation-stone  of  the  method  is  the  spontaneous  emulsion  method  of  Gad. 
W'c  have  previously  seen  how  by  this  method  we  may  determine  when  an 
oil  has  the  proper  percentage  of  fatty  acid  to  give  the  best  spontaneous 
emulsion  under  certain  given  conditions.  After  having  established  the  con- 
ditions under  which  one  can  get  a  good  emulsion  with  a  certain  per  cent 
(S'/O  of  fatty  acid,  it  is  evident  that  we  can  use  this  method  for  determining 
when  an  oil  has  this  percentage  of  fatty  acid,  and  since  the  completeness 
of  the  spontaneous  emulsion  will  be  in  direct  proportion  to  the  nearness 
with  which  the  quantity  of  fatty  acid  in  the  oil  approaches  this  percentage, 
we  have  also  a  method  of  estimating  the  amount  of  increase  of  fatty  acid 
in  any  oil  by  testing  its  spontaneous  emulsibility  from  time  to  time.  For  ex- 
amjile.  let  us  suppose  that  we  have  a  neutral  oil  in  which  fatty  acid  begins 
to  develop,  and  that  this  process  slowly  continues  until  all  the  oil  is  changed 
into  fatty  acid  and  glycerine.  If  the  test  of  spontaneous  emulsibility  be 
applied  to  such  an  oil  by  placing  a  drop  of  it  from  time  to  time  on  carbonate 
of  sodium  solution,  we  get  at  first  no  emulsion  at  all,  and  then  with  the 
development  of  some  fatty  acid  a  slight  emulsion,  then  more  and  more  with 
increasing  quantities  of  acid  until  the  maximum  emulsion  is  reached,  which 
indicates  that  about  five  and  a  half  per  cent,  of  acid  has  been  developed. 
The  enuilsion  then  decreases  with  the  further  increase  of  acid  until  finally 
we  get  no  spontaneous  emulsion  at  all,  which  indicates  about  twelve  per 
cent,  of  acid.  Beyond  this  point  the  increase  of  acidity  cannot  be  measured 
by  spontaneous  emulsion,  but  in  this  particular  and  under  these  circumstances 
the  emulsion  formed  by  shaking  is  of  some  value,  for  good  emulsions  may 
still  be  had  in  this  way  after  too  much  acid  has  been  developed  for  spon- 
taneous emulsion.  But  the  greater  the  amount  of  acid  the  more  shaking 
is  required  to  give  a  good  emulsion,  until  finally  when  all  the  oil  has  been 
changed  into  fatty  acid  and  glycerine  we  get  no  emulsion  at  all,  but  only  a 
cloudiness  due  to  the  insoluble  soap  formed.  In  this  method  we  have  a 
simple  means  of  approximately  estimating  the  increase  of  fatty  acid  in 
an  oil  and  of  determining  when  all  the  oil  has  been  changed  to  acid  and 
glycerine.  This  method  is  not  used  to  determine  the  exact  quantity  of  acid 
which  an  oil  contains,  bin  is  used  rather  to  make  a  com[)arative  estimate 
of  the  amount  of  acid  in  the  same  oil  at  difi:'ereni  times  and  in  different 
oils  at  the  same  time. 

'Handbuch    der    Pliysiologit:,    llcrrmaiin,    BJ.    v. 
Payc    (68 


B.  K.  RACHFORD 


This  method  is  ajijihed  to  the  study  of  the  fat-splitting  properties  of 
pancreatic  juice  in  the  following  manner.  Arrange  a  series  of  watch-glasses 
containing  a  J4  %  solution  of  carbonate  of  sodium.  Take  a  small  test  tube 
of  2  cc.  capacity  and  place  in  it  Yi  cc.  of  pancreatic  juice  and  twice  as  much 
neutral  olive  oil.  Shake  the  tube  and  allow  the  juice  and  oil  to  separate, 
then  pipette  a  drop  of  oil  from  the  surface  and  place  it  on  ihe  soda  solution 
in  watch-glass  I.  Again,  shake  the  tube  and  allow  the  oil  and  juice  to  sepa- 
rate, then  pipette  as  before,  placing  a  drop  of  oil  in  watch-glass  2.  Again 
shake  and  pipette  as  before,  and  repeat  this  process  every  three  or  four 
minutes  until  the  experiment  is  completed.  The  beginning  of  the  experiment 
and  the  time  of  each  pipetting  must  be  carefully  noted.  If  the  pipettings  are 
three  minutes  apart,  then  the  first  drops  of  oil  will  have  been  exposed  three 
minutes  to  the  action  of  pancreatic  juice,  the  second  drop  six  minutes,  the 
third  drop  nine  minutes,  and  so  on.  By  the  amount  of  spontaneous  emulsion 
occurring  in  these  drops  when  placed  on  the  soda  solution  one  can  com- 
paratively estimate  the  quantity  of  fatty  acid  they  contain.  For  example, 
in  an  experiment  such  as  I  have  just  narrated  one  may  find  very  little  emul- 
sion in  glass  1,  more  in  2,  a  fair  emulsion  in  3,  good  in  4,  and  the  maximum 
in  5,  and  then  the  emulsion  gradually  decreases.  By  such  experiments  as 
this  the  fat-splitting  properties  of  pancreatic  juice  can  be  beautifully  dem- 
onstrated, and  an  idea  formed  of  the  rapidity  of  its  action.  There  is  a 
possible  element  of  error  in  this  method  which  had  better  be  spoken  of  here. 
It  would  seem  that  the  alkali  of  the  pancreatic  juice  would  combine  with 
the  fatty  acids  forming  soap  and  in  this  way  the  oil  would  soon  be  emulsified 
in  the  juice  itself  and  not  separate  after  shaking.  This  would  indeed  be  a 
serious  drawback  if  it  actually  occurred,  but  in  truth  it  does  not  occur  until 
late  in  the  experiment  after  we  have  obtained  the  information  we  sought 
by  the  spontaneous  emulsion  method.  It  is  true  that  after  a  large  quantity 
of  acid  has  developed  and  by  repeated  shaking  we  get  an  emulsion  of 
oil  in  the  juice  which  somewhat  interferes  with  the  method.  Although  the 
sodium  in  the  pancreatic  juice  exists  in  the  form  of  a  carbonate,  it  seems 
to  be  peculiarly  associated  with  some  other  substance  which  interferes  witli 
its  combining  with  fatty  acid  in  the  formation  of  soaps.  This  may  be  illus- 
trated by  the  following  interesting  experiment.  Place  in  a  small  test  tube 
drawn  out  like  a  pipette  equal  quantities  of  pancreatic  juice  and  neutral 
olive  oil,  3/  cc.  each.  Shake  the  tube  and  set  aside  for  twenty-four  hours. 
.'\t  the  expiration  of  this  time  break  the  pipette  point  and  allow  the  contents 
of  the  tube  to  escape  slowly  through  the  opening  thus  formed  in  the  bottom 
.  of  the  tube.  The  pancreatic  juice,  being  at  the  bottom,  is  the  first  to  escape, 
and  it  is  clear  and  strongly  alkaline ;  then  comes  the  oil  which  formed  the 
upper  layer,  and  it  is  strongly  acid.  Here  we  have  a  rancid  oil  and  an  alka- 
line fluid  in  contact  for  twenty-four  hours  with  very  little  soap  formation. 
This  experiment  clearly  indicates  that  something  interferes  with  the  forma- 
tion of  soap  from  the  alkalies  of  the  pancreatic  juice.  This  is  a  plausible 
explanation  of  why  the  element   of  error  caused  by  soap   formation  does 


RANSOHOFF  MFMORIAL  VOLUMF 


not  iiUerfcri'  with  the  iiractical  applicatiiiii  (if  the  method.  But  even  the 
small  element  of  error  which  is  introduced  hy  soaji  formation  may  be  re- 
duced to  a  minimum  hy  usins:;  small  quantities  of  juice  and  three  or  four 
times  as  much  oil,  and  in  that  way  the  Cjuantity  of  soda  is  greatly  reduced 
and  the  action  of  the  juice  is  but  slightly  retarded.  This  latter  seems  a 
strange  statement,  yet  I  have  found  in  my  experiments  that  within  the 
limits  named,  the  same  quantity  of  juice  splits  large  quantities  of  oil  almost 
as  readily  as  small.  In  passing,  let  me  again  call  attention  to  the  experiment 
above  narrated  as  a  simple  and  striking  lecture  experiment.  The  alkalinity 
of  the  juice  and  the  acidity  of  the  oil  as  it  follows  through  the  same  open- 
ing may  be  demonstrated  by  litmus  paper  or  solution.  \\'ith  these  details 
as  to  method  we  are  prepared  to  consider  pancreatic  juice  and  its  action 
on  neutral  fats. 

1st.  The  pancreatic  juice  of  the  rabbit  is  alkaline  and  remains  so  for 
some  time  after  it  is  removed.  On  two  occasions  I  tested  juice  that  had 
stood  exposed  at  room  temperature  for  twenty-four  hours  and  found  it 
alkaline  and  physiologically  active.  Different  specimens  of  pancreatic  juice 
may  vary  in  physiological  activity.  As  a  rule,  the  juice  obtained  from  a 
fistula  that  has  been  acting  several  hours  is  not  as  active  as  juice  from  the 
same  fistula  obtained  soon  after  the  operation. 

2nd.  If  pancreatic  juice  be  shaken  with  neutral  olive  oil,  the  oil  rapidly 
lakes  on  an  acid  reaction.  That  this  acidity  is  due  to  fatty  acid  is  show-n 
hy  the  facts  that  all  the  acid  may  be  extracted  with  ether  and  the  oil  made 
emulsible  by  its  presence.  The  gradual  yet  rapid  development  of  fatty  acid 
by  the  action  of  pancreatic  juice  on  neutral  olive  oil  may  be  beautifully 
demonstrated  by  pipetting  drops  of  oil  at  intervals  from  the  surface  of  a 
mixture  of  pancreatic  juice  and  neutral  olive  oil  and  jilacing  them  on  a 
J4  %  solution  of  carbonate  of  sodium  in  a  series  of  watch-glasses.  Soon 
we  have  a  slight  emulsion,  then  more  and  more  until  the  maximum  is  reached, 
then  the  amount  of  emulsion  becomes  less  and  less  as  too  much  fatty  acid 
is  developed,  until  finally  we  have  no  spontaneous  emulsion  at  all.  That  an 
excess  of  fatty  acid  is  the  cause  of  the  decrease  and  cessation  of  spontaneous 
emulsion  may  be  demonstrated  as  follows.  Take  a  drop  of  oil  from  a  mixture 
of  oil  and  pancreatic  juice  after  it  has  passed  the  limits  of  spontaneous 
cmulsibility  and  mix  it  with  neutral  olive  oil,  and  the  mixture  is  spontan- 
eously emulsible.  In  one  experiment,  for  example,  I  took  one  droj)  of  oil 
that  had  passed  the  stage  of  spontaneous  emulsibility  and  mixed  it  with 
four  drops  of  a  neutral  olive  oil,  and  one  drop  of  the  mixture  on  soda  solu- 
tion gave  a  beautiful  spontaneous  emulsion.  Here  one  drop  of  the  oil 
acted  on  by  the  juice  contained  sufficient  fatty  acid  to  make  five  drops  of 
oil  spontaneously  emulsible,  that  is,  to  give  five  drops  of  oil  about  5>^  % 
of  fatty  acid.  The  drop  of  oil  acted  on  by  the  juice  must  therefore  have 
contained  about  30%  of  fatty  acid  and  the  time  required  to  develop  it  was 
thirty-five  minutes.    Since  30/(    of  acid  is  so  quickly  develoi)ed,  it   seems 

Page   !,-,0 


B.  K.  RACHFORD 


a  fair  inference  that  the  prolonged  action  of  the  juice  would  change  all  the 
oil  fatty  acid  and  glycerine,  and  such  in  fact  is  found  to  be  the  case. 

3rd.  All  the  oil  is  split  into  fatty  acid  and  glycerine  by  from  one  to 
two  hours'  action  of  the  pancreatic  juice — time  varies  with  the  specimen 
of  the  juice.  This  may  be  shown  by  pipetting  such  fatty  matter  from  the 
surface  of  the  juice  and  shaking  it  with  soda  solution  and  no  emulsion  will 
result,  simply  a  little  clouding  such  as  occurs  when  fatty  acid  is  shaken  with 
soda  solution.  But  if  one  drop  of  this  same  fatty  matter  be  mixed  with  si.x 
or  eight  drops  of  neutral  olive  oil,  this  mixture  will,  on  being  shaken  with 
soda  solution,  give  a  good  emulsion.  This  experiment  is  best  performed 
by  adding  a  small  quantity  of  bile  to  the  juice  before  adding  the  oil.  The 
bile  does  not  interfere  with  the  fat-splitting  action  of  the  juice,  but  it  does 
interfere  with  the  formation  of  an  emulsion,  and  for  that  reason  the  oil 
and  juice  continue  to  separate  after  shaking. 

4th.  The  time  required  for  pancreatic  juice,  acting  in  glass  tubes  at 
room  temperature,  to  develop  sufficient  fatty  acid  (5>^%)  in  neutral  olive 
oil  to  give  the  maximum  spontaneous  emulsion  varies  with  different  spec- 
imens of  the  juice  and  with  the  amount  of  shaking  to  which  the  juice  and 
oil  are  subjected,  but  the  average  time  as  taken  from  my  experiments  was 
twenty  minutes.  In  very  active  specimens  of  the  juice  it  occurred  as  early 
as  seven  minutes,  and  in  very  poor  specimens  as  late  as  sixty  minutes.  I 
also  found  that  the  juice  did  not  act  more  rapidly  in  a  basin  of  intestine  than 
in  the  test  tubes.  In  these  experiments  the  resected  intestine  containing  the 
pancreatic  papilla  was  held  by  a  fenestrated  quadrilateral  clamp  made  for 
the  purpose,  and  into  the  basin  of  the  intestine  thus  formed  the  pancreatic 
juice  would  ooze.  Neutral  olive  oil  was  dropped  into  this  basin  and  mixed 
with  the  pancreatic  juice,  and  this  oil  did  not  become  spontaneously  emul- 
sible  more  quickly  than  the  oil  in  the  test  tubes,  but  the  conditions  here  are 
also  far  from  resembling  those  occurring  in  the  normal  duodenum,  and  the 
average  rate  of  fat-splitting  as  estabhshed  by  these  experiments  is  probably 
considerably  below  the  rate  at  which  fats  are  split  in  the  duodenum.  It  is 
probable  that  the  time  required  by  the  most  active  juice  p.iore  nearly  rep- 
resents the  rapidity  of  action  of  pancreatic  juice  in  the  duodenum. 

5th.  The  action  of  pancreatic  juice  on  most  of  the  fats  is  rapid  and 
complete. 

Castor  oil  is  a  notable  exception  to  this  rule,  as  only  a  very  small  quan- 
tity of  acid  is  developed  in  it  Ijy  the  action  of  pancreatic  juice  for  five  hours 
at  2>7°  C.  Castor  oil  is  therefore  practically  indigestible  and  this  may  in 
part  account  for  its  cathartic  action. 

Pancreatic  juice  acts  slowly  on  fats  which  have  a  melting  point  above 
body  temperature,  but  it  is  an  interesting  physiological  fact  that  their  solidity 
at  body  temperature  does  not  prevent  their  being  split.  Spermaceti  for  exam- 
ple, the  melting  point  of  which  is  above  38°  C,  is  slowly  split  by  the  action 
of  the  pancreatic  juice. 


RANSOHOFF  MEMORIAL  VOLUME 


6th.  As  T  have  previously  said,  the  pancreatic  juice  of  the  rabbit  and 
neutral  olive  oil  when  shaken  together  show  very  slight  tendency  to  the 
formation  of  an  emulsion,  and  it  is  only  after  considerable  acid  has  de- 
veloped that  repeated  shaking  will  give  a  mixture  resembling  an  imperfect 
emulsion.  But  if  we  mix  and  shake  at  intervals  one  part  of  neutral  olive 
oil  and  one  part  of  pancreatic  juice  for  about  fifteen  minutes,  and  then  add 
six  parts  of  soda  solution,  we  get  at  once  an  apparently  good  emulsion. 
This  emulsion  does  not  remain  good ;  it  always  in  the  course  of  an  hour  or 
two  clears  by  creaming,  when  the  whole  mixture  will  be  found  to  have  a 
strong  acid  reaction  due  to  the  large  quantity  of  fatty  acid  developed.  What- 
ever may  be  the  explanation  of  the  clearing  of  this  pancreatic  emulsion,  the 
fact  remains  that  an  emulsion  will  form  in  the  presence  of  pancreatic  juice 
if  carlionatc  of  sodium  solution  be  added,  but  it  does  not  remain  permanent. 

7lh.  A  permanent  pancreatic  emulsion  may  be  formed  by  pipetting  the 
oil  from  the  surface  of  a  tube  containing  oil  and  juice  and  shaking  it  with 
the  carbonate  of  sodium  .solution.  The  emulsion  formed  in  this  way  remains 
very  much  the  same  for  an  indefinite  length  of  time.  In  this  experiment  the 
oil  is  made  emulsible  by  the  action  of  the  juice  and  is  then  separated  from 
it  and  emulsified  with  the  soda  solution;  the  emulsion  itself  contains  no 
])ancreatic  juice  and  therefore  does  not  clear.  This  permanent  pancreatic 
emulsion  reacts  to  emulsion  destroying  agents  and  soap  dissolvers  very  like 
a  fatty  acid  emulsion  made  with  rancid  oil  and  sodium  solution.  For  exam- 
ple, it  is  not  destroyed  by  the  addition  of  bile  or  fatty  acids,  but  is  destroyed 
by  mineral  acids,  resisting  hydrochloric  better  than  nitric  and  sulphuric 
acids.  The  pancreatic  emulsion  also  resembles  the  simple  rancid  oil  emul- 
sion in  that  an  appreciable  length  of  time  must  elapse  after  its  formation 
before  it  reaches  its  greatest  degree  of  stability.  This  may  be  demonstrated 
by  adding  bile  in  excess  immediately  after  the  formation  of  the  emulsion, 
when  it  destroys  the  emulsion  by  creaming,  but  if  the  bile  be  added  later 
no  such  eiifect  is  produced.  It  also  resembles  the  rancid  oil  emulsion  in 
that  it  cannot  form  at  all  in  the  presence  of  bile. 

The  most  important  application  of  the  method  I  have  described  is  in 
obtaining  comparative  information  concerning  the  fat-splitting  properties 
of  pancreatic  juice.  This  application  of  the  method  may  best  be  explained 
by  detailing  an  experiment  inquiring  into  the  difference  in  the  rapidity  of 
action  of  pancreatic  juice  at  room  (18°  C.)  and  at  body  teinperature  (37°). 

Arrange  two  rows  of  watch-glasses  containing  a  J4  %  carbonate  of  so- 
dium solution.  Take  two  small  test  tubes,  ]/i  c.c.  of  the  same  pancreatic 
juice  in  each,  and  to  each  tube  add  Yi  c.c.  of  neutral  olive  oil.  Shake  both 
tubes  equally  and  place  one  of  them  (A)  in  a  sand  bath  kept  in  an  oven 
at  2i7°  C.  and  leave  the  other  (B)  at  room  temperature.  At  the  expiration 
of  three  minutes  pipette  a  drop  of  oil  from  A  and  place  it  in  watch-glass 
1.  row  1  ;  then  as  quickly  as  possible,  with  a  clean  pipette,  take  a  drop  from 
]'.  and  place  it  in  watch-glass  1,  row  2.  Both  tubes  are  shaken  and  replaced 
and  at  the  expiration  of  three  minutes  a  drop  is  again  i>ii)etted  from  the  sur- 

Pa,jc   .}7i 


A'.  RACHFORD 


face  of  each.  That  from  A  is  placed  in  row  1,  that  from  B  in  row  2.  This 
process  is  repeated  again  and  again  to  the  end  of  the  experiment.  At  the 
close  of  the  experiment  it  will  be  found  that  the  emulsion  occurs  almost 
twice  as  quickly  in  row  1  as  in  row  2.  The  three-minute  drop  of  oil  from 
A  gives  as  good  an  emulsion  as  the  six-minute  drop  of  oil  from  B,  and  the 
nine-minute  drop  of  oil  from  A  gives  the  same  emulsion  as  the  eighteen- 
minule  drop  of  oil  from  B.  Since  these  tubes  were,  apart  from  the  tempera- 
ture, treated  as  nearly  alike  as  possible,  we  infer  that  pancreatic  juice  acts 
about  twice  as  rapidly  at  37°  C.  as  it  does  at  18°  C.  The  average  ratio  of  in- 
creased rapidity  of  action,  taken  from  my  experiments,  was  as  one  to  one  and 
eight-tenths. 

Whatever  objections  may  be  urged  against  the  absolute  accuracy  of  the 
figures  obtained  by  this  method,  the  same  do  not  apply  to  the  comparative 
accuracy  of  these  figures.  Even  though  we  may  not  be  able  by  this  method 
to  estimate  the  amount  of  acid  produced  by  pancreatic  juice  in  nine  min- 
utes acting  at  37°  C,  we  do  know  by  this  method,  whatever  this  amount  may 
be,  that  it  requires  one  and  eight-tenths  times  as  long  for  pancreatic  juice 
to  produce  the  same  amount  at  18°  C.  In  comparative  experiments  such 
as  this  it  is  not  necessary  nor  practicable  to  have  an  equal  length  of  time 
between  the  pipettings,  but  it  is  important  that  the  tubes  should  be  shaken 
at  as  nearly  the  same  time  and  pipetted  at  as  nearly  the  same  time  as  pos- 
sible, so  that  the  oil  drops  to  be  compared  by  spontaneous  emulsibility  may 
have  been  exposed  to  the  action  of  the  juice  for  the  same  length  of  time, 
thus  establishing  the  comparative  accuracy  of  the  results. 

The  great  value  and  wide  appliction  of  this  method  is  seen  in  the  study 
of  the  influence  of  bile  and  other  agents  on  the  fat-splitting  action  of  i)an- 
creatic  juice. 

Bile  alone  does  not  split  fats.  This  seems  a  well  established  ])hysiological 
fact,  which  may  be  confirmed  by  shaking  neutral  olive  oil  and  bile  in  a  test- 
tube  and  pipetting  the  oil  at  intervals  to  the  surface  of  a  carbonate  of  sodium 
solution  as  in  previous  pancreatic  experiments,  when  it  will  be  found  that 
oil  shaken  with  bile  for  twenty-four  hours  does  not  become  emulsible.  The 
value  of  this  method  is  here  most  conspicuous  as  the  emulsibility  of  the  oil 
could  not  be  tested  in  the  presence  of  the  bile,  because  the  bile  would  pre- 
vent an  emulsion  even  if  the  fatty  acid  had  been  developed.  But  in  this 
method  the  oil  is  separated  from  the  bile  after  they  have  been  in  contact 
twenty-four  hours  and  its  emulsibility  tested,  and  in  this  point  lies  the  great 
value  and  wide  application  of  the  method,  since  the  very  agents,  such  as 
bile  and  hydrochloric  acid,  which  have  the  greatest  influence  on  the  fat- 
splitting  action  of  pancreatic  juice,  are  the  agents  which  interfere  with  the 
formation  of  emulsions. 

Fresh  rabbit  bile  removed  from  the  gall  bladder  was  used  in  all  my 
experiments. 

In  every  comparative  experiment  the  pancreatic  juice  which  had  been 
collected  in  a  single  tube  was  divided  into  two,  three  or  four  equal  ])arts 


RANSOM  OFF  MEMORIAL  VOLUME 


according  to  the  number  of  tubes  used  in  the  experiment.    The  bile  was  also^ 
shaken  and  divided  just  previous  to  the  experiment.    In  this  way  I  could 
be  reasonably  sure  that  I  was  working  with  the  same  bile  and  same  pan- 
creatic juice  in  all  the  tubes. 

P.y  the  methods  described  I  reached  the  following  conclusions. 

1st.  An  equal  amount  of  fresh  rabbit's  bile  will,  on  being  added  to 
ral)hit's  pancreatic  juice,  greatly  hasten  its  fat-splitting  action  in  the  ratio 
of  three  and  one-fifth  to  one.  In  experiments  of  this  kind,  tube  A  contains 
,'3  cc.  of  pancreatic  juice  and  J/2  cc.  of  neutral  olive  oil,  and  tube  B  contains 
3<5  cc.  pancreatic  juice  and  Yi  cc.  bile  and  ^-5  cc.  of  neutral  olive  oil.  These 
tubes  are  treated  alike  and  the  emulsibility  of  the  oil  is  tested  from  time  to 
time  as  previously  described.  In  this  way  the  comparative  rapidity  with 
which  fatty  acid  is  developed  in  the  oils  may  be  determined.  It  is  evident 
that  in  every  experiment  we  can  have  two  sets  of  figures  from  which  to 
make  our  average,  viz.  the  time  required  for  the  beginning  and  the  time 
required  for  the  maximum  of  spontaneous  emulsion.  In  my  general  averages 
I  have  used  both  sets  of  figures,  striking  an  average  between  them. 

2nd.  An  equal  quantity  of  a  >4%  solution  of  hydrochloric  acid  will, 
on  being  added  to  pancreatic  juice,  retard  its  fat-splitting  action  in  the  ratio 
of  two-thirds  to  one. 

3rd.  A  mixture  of  equal  quantities  of  bile  and  a  %%  hydrochloric  acid 
solution  will,  on  being  added  to  pancreatic  juice,  greatly  hasten  its  fat-split- 
ting action  in  the  ratio  of  four  to  one.  The  bile  not  only  neutralizes  the 
retarding  influence  of  the  hydrochloric  acid  on  the  fat-splitting  properties 
of  the  juice,  but  it  really  acts  more  powerfully  in  hastening  the  action  of  the 
juice  when  in  the  presence  of  this  acid  than  it  does  when  acting  alone.  The 
contents  of  a  series  of  tubes  will  best  explain  the  class  of  experiments  upon 
which  this  statement  is  based. 

Tube  A  contains  Y  cc.  pancreatic  juice  and  %  cc.  neutral  olive  oil. 
Tube  P)  contains  l-\i  cc.  of  pancreatic  juice,  ^  cc.  of  bile  and  %  cc.  neutral 
olive  oil.  Tube  C  contains  '/j  cc.  of  pancreatic  juice,  Vo  cc.  of  bile, 
\{;  CC.  of  a  J4   %  hydrochloric  acid  solution,  and  %  cc.  of  neutral  olive  oil. 

Three  rows  of  watch-glasses  containing  soda  solution  having  been  ar- 
ranged for  the  reception  of  the  oil  drops,  the  tubes  are  now  shaken  and 
pipetted  as  in  previous  experiments  and  the  time  and  the  result  are  carefully 
noted.  In  row  1  containing  the  oil  drop  from  A,  the  emulsion  begins  in 
eight  minutes,  and  reaches  the  maximum  in  twenty  minutes.  In  row  2  con- 
taining the  oil  from  B,  the  emulsion  begins  in  two  and  a  half  minutes  and 
reaches  the  maximum  in  six  and  a  quarter  minutes.  In  row  3  containing 
the  oil  drop  from  C,  the  emulsion  begins  in  two  minutes  and  reaches  the 
maxinuini  in  five  minutes.  These  figures  are  the  averages  of  a  number  of 
exiierimcnts. 

4lh.  If  an  e(|ual  quantity  of  a  3%  solution  of  glycocholate  of  soda 
be  mixed  with  pancreatic  juice  it  hastens  the  fat-splitting  action  of  the  juice 
in  llie  ratio  of  two  and  one-fifth  to  one. 


B.  K.  RACHFORD 


5th.  A  mixture  of  e(|ual  (|uantilics  of  a  i^'/<  solution  of  glycocholate 
of  soda  and  a  '4%  solution  of  liydrochloric  acid  will,  on  being  added  in 
equal  quantities  to  pancreatic  juice,  hasten  its  fat-splitting  action  in  the 
ratio  of  two  and  one-third  to  one. 

'I'he  glycocholate  of  soda  solution,  like  the  bile,  not  only  neutralized  the 
retarding  influence  of  hydrochloric  acid  on  the  fat-splitting  action  of  the 
juice,  but  it  really  acts  more  powerfully  in  hastening  the  action  of  the  juice 
when  in  the  presence  of  the  acid  than  it  does  when  acting  alone.  It  must 
also  be  noted  that  the  glycocholate  of  soda  does  not  act  as  powerfully  in 
hastening  the  fat-splitting  action  of  the  juice  as  the  bile  does.  In  the  pres- 
ence of  bile  the  juice  acts  three  and  one-fifth  times  as  rapidly  as  it  does 
alone,  and  in  the  presence  of  a  three  per  cent,  solution  of  glycocholate  of 
soda  it  acts  two  and  a  fifth  times  as  rapidly.  In  the  presence  of  bile  and  hy- 
drochloric acid  it  acts  four  times  as  rapidly,  and  in  the  presence  of  glyco- 
cholate of  soda  and  hydrochloric  acid  it  acts  two  and  four-fifths  as  rapidly. 
From  this  I  infer  that  this  property  of  the  bile  is  chiefly  but  not  wholly 
due  to  the  glycocholate  of  soda  it  contains.  The  class  of  experiments  by 
which  these  conclusions  were  reached  is  illustrated  in  Plate  I,  which  is  in 
part  reproduced  from  a  photograph. 

6th.  If  one  part  of  pancreatic  juice  be  diluted  with  five  parts  of  a 
y^  %  carbonate  of  sodium  solution  its  fat-splitting  properties  will  be  greatly 
retarded — in  the  ratio  of  one  to  eight — and  further  dilution  with  soda  solu- 
tion gives  greater  retardation,  this  property  of  the  juice  being  practically 
destroyed  when  it  is  ten  times  diluted  with  this  strength  of  soda  solution. 
That  this  retarding  influence  is  due  to  the  soda,  and  not  to  the  dilution,  is 
shown  by  the  fact  that  if  pancreatic  juice  be  diluted  with  five  parts  of  dis- 
tilled water,  its  fat-splitting  action  is  very  slightly,  if  at  all.  retarded. 

The  retarding  influence  of  soda  solution  may  be  shown  by  the  same  kind 
of  experiments  used  to  show  the  influence  of  bile,  hydrochloric  acid  etc. 
on  the  fat-splitting  properties  of  pancreatic  juice.  But  it  seems  possible 
that  there  might  be  considerable  cause  of  error  in  this  class  of  experiments, 
because  of  the  presence  of  soda  solution  in  one  of  the  tubes.  In  an  exper- 
iment of  this  kind,  for  example,  one  tube  contains  Vi  cc.  of  pancreatic  juice 
and  %  cc.  of  neutral  olive  oil,  the  other  contains  in  addition  to  the  same 
quantity  of  juice  and  oil  %  cc.  of  soda  solution.  In  pipetting  oil  from  the 
surface  of  two  such  tubes  to  test  its  spontaneous  emulsibility,  will  not  the 
result  be  greatly  vitiated  by  the  soda  solution  in  one  of  the  tubes,  neutralizing 
the  fatty  acid  as  soon  as  formed?  Theoretically  this  would  seem  to  be  an 
important  source  of  error,  but  practically  it  is  not  of  very  great  importance, 
since  the  results  obtained  by  this  method  correspond  closely  to  those  obtained 
by  another  method  which  has  not  this  source  of  error.  The  following 
experiment  will  illustrate  this  method.  Take  two  small  glass  tubes.  In  one 
place  Yi  cc.  of  pancreatic  juice  and  ^3  cc.  of  neutral  olive  oil.  Shake  four 
or  five  minutes  and  add  %  cc.  of  soda  solution  and  an  immediate  emulsion 
will  result.  To  the  other  tube  add  Yi  cc.  pancreatic  juice  and  >fi  cc.  of  neutral 

Page  7,75 


RANSOM  OFF  MEMORIAL  VOLUME 


olive  oil  and  %  cc.  of  soda  solution.  Shake,  and  the  emulsion  will  not  appear 
for  thirty  or  thirty-five  minutes.  In  the  first  tube,  the  pancreatic  juice  acting 
alone  on  the  neutral  oil  produced  enough  acid  in  four  or  five  minutes  to 
make  the  oil  emulsible  on  shaking  it  with  the  soda  solution.  L!ut  in  the 
tube  2,  the  presence  of  the  soda  solution  retarded  the  action  of  the  juice  so 
that  it  required  thirty  minutes  to  produce  suft:cient  fatty  acid  to  give  an 
emulsion.  Carbonate  of  soda  solution  therefore  retards  the  fat-splitting 
action  of  pancreatic  juice  in  the  ratio  above  given. 

In  the  accompanying  diagram  I  have  taken  a  line  twenty  millimetres 
long  to  represent  the  working  power  of  pancreatic  juice  acting  alone  at 
room  temperature.  The  other  lines  represent  the  comparative  working  power 
of  pancreatic  juice  under  the  conditions  named,  and  were  obtained  from 
averaging  all  my  experiments. 

DL\GRAM  SHOWING  THE  INFLUENCE  OF  BILE  .\XD  OTHER  .\GENTS 
ON  THE  F.'SiT-SPLITTlNG  PROPERTIES  OF  PANCRE.A'I'IC  JUICE 

Pancreatic  juice  at   18'^C. 

20  Mil.  I 

Pancreatic  juice  at  37°C. 

36  Mil.     ?.-, 

Pancreatic  juice  at  18°   C.  and  HCl. 

13  Mil.     % 

Pancreatic  juice  at  18°  C.  and  glycocholate  of  soda. 

44  Mil.     Vr, 


Pancreatic  juice  at  18°  C.  and  gl\ 
56  Mil.      


Pancreatic  juice  at  18°   C.  and  bil 
64  Mil.      ^^^^^^->- 


Pancreatic  juice  at  18°  C.  and  bile  and  HCl. 
80  Mil.      ^—^—.-...^^^^-^^^— 


The  above  diagram  and  accompanying  figures  are  offered  as  the  clearest 
and  briefest  manner  of  expressing  the  difference  in  the  rapidity  of  action 
of  the  various  mixtures.  It  is  not  even  hoped  that  these  figures  are  abso- 
lutely correct,  but  it  is  my  belief  that  relatively  they  are  approximately  cor- 
rect, and  therefore  have  an  all  important  bearing  on  the  pancreatic  digestion 
of  fats.    \\'e  may  summarize. 

(1)  Pancreatic  juice  can.  acting  alone,  do  a  certain  piece  of  work  in 
.V  minutes,  viz.  develop  in  neutral  olive  oil  a  sufficient  quantity 
of  fatty  acid  to  give  the  best  spontaneous  emulsion. 

(2)  Pancreatic  juice  acting  in  the  presence  of  five  parts  oi  a  %% 
carbonate  of  soda  solution  will  require  8.r  minutes  to  do  the  same 
work,  and  in  the  presence  of  ten  parts  of  the  ^.ame  solution  its 

action   will   be   almost   destroved. 


B.  K.  RACHFORD 


(3)  Pancreatic  juice  acting  in  the  presence  of  an  equal  quantity  of 
a  ,'4%  solution  of  hydrochloric  acid  will  require  %x  minutes  to 
do  the  same  work. 

(4)  Pancreatic  juice  acting  in  the  presence  of  an  et|ual  (|uantity  of 
mixture  of  bile  and  a  %%  hydrochloric  acid  solution  will  require 
only  y^.v  minutes  to  do  the  same  work. 

Froiu  the  last  two  propositions  it  would  follow  that,  if  bile  be  added 
to  pancreatic  juice  which  is  acting  in  the  presence  of  hydrochloric  acid,  the 
fat-s|ilitting  action  of  the  juice  will  be  hastened  as  %  to  Y^  or  as  six  to  one, 
and  reversely,  that  if  the  bile  be  withdrawn  or  cut  off  from  pancreatic  juice 
which  has  previously  been  acting  in  the  presence  of  both  bile  and  hydro- 
chloric acid,  the  fat-splitting  properties  of  the  juice  will  be  retarded  as 
six  to  one. 

.\PI'LIC.\T10.\  f)l'  THliSH  PRIXCIJ'LES  TO  THl':  IXTl^STIX.XL  DICHSTIUX 
OF  F.ATS 

It  is  needless  to  say  that  my  experiments  were  planned  with  the  idea  of 
placing  pancreatic  juice  under  conditions  as  nearly  as  possible  resembling 
those  under  which  it  acts  in  the  intestine.  The  influence  of  a  ^4  %  solution 
of  HCl  was  studied  because  of  the  presence  of  this  acid  in  the  duodenum 
where  the  pancreatic  juice  comes  in  contact  with  the  fats. '  The  influence 
of  bile  and  of  a  mixture  of  bile  and  hydrochloric  acid  were  studied  for  the 
same  reason.  The  influence  of  dilution  with  a  ^4  %  solution  of  carbonate 
of  sodium  was  studied  because  it  was  thought,  that,  as  the  pancreatic  juice 
passed  downward  into  the  small  intestine,  it  might  be  subjected  to  some  such 
influence,  since  the  succus  entericus  contained  this  percentage  of  carbonate 
of  soda.  'J'he  conclusions  therefore  to  which  I  have  arrived  must,  if  true, 
have  a  very  important  bearing  in  the  explanation  of  the  intestinal  digestion 
of  fats.  I  infer  from  my  experiments  that  in  the  duodenum  the  mixture 
of  bile  tnd  hydrochloric  acid  furnishes  the  best  known  conditions  for  ex- 
pediting the  fat-splitting  action  of  pancreatic  juice,  and  the  cutting  olif  of 
the  bile  would  retard  the  fat-splitting  action  of  the  juice  six  times.  It  may 
also  be  of  some  physiological  importance  to  note  that  the  agents  bile  and 
HCl  which  expedite  the  fat-s|)litting  absolutely  preclude  the  formation  of 
emulsions.  The  duodenum  therefore  olTers  the  most  favourable  conditions 
for  the  splitting  of  the  fats  and  the  most  unfavourable  for  their  emulsifica- 
tion.  In  the  jejunum  and  ileum  these  conditions  seem  to  be  exactly  reversed. 
The  intestinal  juice  containing,  as  it  does  34  %'  of  carbonate  of  soda,  would 
not  only  furnish  the  conditions  for  the  spontaneous  emulsification  of  the 
rancid  fats,  but  would  also  retard  the  fat-splitting  action  of  the  pancreatic 
juice.  I  do  not  wish  to  express  the  belief  that  intestinal  juice  jilays  just 
such  a  role  as  this  in  the  intestinal  digestions  of  fats,  but  only  oiTcr  it  as 
a  deduction  from  te^t  lube  experiments,  thinking  it  may  lia\e  some  physio- 
lo<>ica!  bcarint'. 


RANSOHOFF  MEMORIAL  VOLUME 


From  my  experiments  I  infer  that  pancreatic  juice  must  act  very  rapidly 
under  the  favourable  conditions  found  in  the  duodenum.  In  some  of  my 
experiments  at  room  temperature,  good  specimens  of  pancreatic  juice  aided 
by  the  presence  of  bile  and  hydrochloric  acid  produced,  in  neutral  olive  oil, 
5K'  %  of  fatty  acid  in  two  minutes.  At  body  temperature  this  work  would 
have  been  accomplished  in  one  minute,  and  under  tlie  favourable  conditions 
ofifered  by  the  duodenum  it  would  probably  have  been  done  in  even  less 
time. 

This  rapidity  of  action  of  pancreatic  juice  is  of  great  physiological  im- 
portance since  it  is  evident  that  at  this  rate,  all  the  fats  would  be  split  into 
fatty  acid. and  glycerine  in  the  time  required  for  intestinal  digestion,  unless 
this  action  of  the  juice  was  checked  or  retarded  in  some  manner. 

IMPORTAXCE  OF  BILE  IX  THE  IXTESTIXAL  DIGESTIOX  OF  FATS 
The  various  conditions  which  have  an  influence  on  the  intestinal  diges- 
tion of  fats  have  been  developed  by  natural  selection,  and  so  far  as  we 
know  they  are  the  best  for  the  purposes  they  serve.  The  comparative  im- 
mobility of  the  duodenum,  its  close  attachment  to  the  head  of  the  pancreas, 
its  horse-shoe  shape,  all,  no  doubt,  have  an  influence  on  the  rate  of  passage 
of  food  stufTs.  This  rate,  which  is  chiefly  controlled  by  these  and  other  ana- 
tomical conditions,  was  established  to  accord  with  normal  digestive  functions, 
and  by  this  mechanism  the  fats  are  exposed  to  the  action  of  pancreatic 
juice  just  long  enough  to  allow  for  whatever  action  that  juice  may  have 
in  fat  digestion.  Let  us  suppose  that  under  normal  conditions  the  fats  are 
exposed  in  the  duodenum  to  the  action  of  pancreatic  juice  for  x  minutes,  and 
that  this  time  is  just  sufficient  to  allow  for  whatever  fat-splitting  is  nec- 
essary at  this  point.  Now  if  the  bile  be  cut  oiT,  the  rate  of  passage  of  the 
food  stuffs,  which  is  chiefly  controlled  by  anatomical  conditions,  remaining 
the  same,  the  fat  would  still  be  exposed  to  the  action  of  the  juice  for  only 
X  minutes.  But  since  in  the  absence  of  the  bile  the  pancreatic  juice  is  able 
to  accomplish  only  'i,  of  the  fat  splitting  which  it  normally  does  it  would 
follow  that  the  fats  would  pass  with  only  lis  of  the  amount  of  splitting  that 
normally  occurs,  and  since  the  splitting  of  the  fat  is,  as  recognized  by  all 
physiologists,  a  necessary  preliminary  step  in  fat  digestion,  it  would  follow 
that  the  fats  would  pass  in  great  part  undigested.  This  gives  to  bile  a  most 
important  and  definite  position  among  the  juices  which  assit  in  fat  digestion, 
since  we  have  here  pointed  out  at  least  one  of  the  ways  in  which  it  exerts  its 
wonderful  influence  in  fat  digestion.  Physiologists  have  been  led  to  believe 
through  much  clinical  and  experimental**  evidence  that  the  bile  was  necessary 
to  fat  digestion.  How  and  where  it  acted  has  been  one  of  the  greatest  of  phy- 
siological mysteries.  The  experiments  of  W'estinghausen"  seemed  to  show 
that  bile  promoted  the  passage  of  the  fats  through  membranes,  and  this  was 
thought  by  some  i)hysiologists  to  have  a  bearing  on  the  absorption  of  fats. 

SOf  special  interest  are  the  recent  experiments  of  A.  Dastre  in  tlic  Arch,  de  Pliysiologie  et 
PatlioloRie.    Paris. 

"Archiv.  fiir  Anal.   u.  Phys.,   lf<73. 


B.  K.  RACHFORD 


I'.ul  since  thf  ])ul)licati<)n  of  Groeper'"  denying  that  bile  had  any  such  action 
we  have  been  quite  a1>  much  at  sea  as  ever  in  explaining  the  action  of  bile 
in  fat  digestion. 

I  wish  to  thank  Prof.  Gad  for  his  kindness  and  advice  during  the  prose- 
cution of  these  studies. 


ADHERENT  HERNIAS  OF  THE  LARGE  INTESTINE.* 
By  J.  Louis  Ransohokf.  M.  D. 

Cincinnati. 

Sliding  hernia  of  the  sigmoid  is  a  subject  whicli  as  a  rule  does  not  receive 
the  attention  it  merits.  In  most  text-books  on  surgery,  even  in  some  of 
the  treatises  on  hernia,  it  is  barely  mentioned.  Though  uncommon,  it  is  one 
of  the  most  important  forms  of  hernia,  its  importance  lying  in  its  recognition 
during  operation.  If  unrecognized,  proper  operative  steps  cannot  be  insti- 
tuted, and  the  viability  of  the  bowel  may  be  jeopardized. 

Since  the  first  accurate  description  by  Scarpa  in  1812,  it  has  been  vari- 
ously known  as  adherent  hernia  of  the  large  intestine,  hernia  with  incom- 
plete sac  or  sliding  hernia,  the  hernie  par  glissmentc  of  French  authors.  As 
I  hope  to  show,  the  only  proper  designation  is  adh.erent  hernia  of  the  large 
intestine,  the  other  terms  being  misnomers,  based  on  faulty  conception  of 
pathogenesis. 

The  most  widely  accepted  theory  is  that  this  form  of  hernia  occurs  by 
the  sliding  of  the  gut  on  the  posterior  peritoneum.  Before  going  further 
it  is  essential  to  describe  the  appearance  of  the  unreduced  hernia  in  the 
opened  sac.  The  contents  of  the  sac  are  either  caecum  and  ascending  colon 
in  right  hernias,  or  ileopelvic  colon  (commonly  called  sigmoid)  in  left  her- 
nias; very  rarely  the  transverse  colon.  The  sac,  well  formed  and  complete 
on  its  anterior  aspect,  is  seemingly  deficient  behind,  the  bowel  being  tightly 
adherent  to,  and  apparently  incorporated  in,  the  posterior  wall  of  the  sac; 
hence  the  designation,  hernia  with  incomplete  sac.  Fig.  1  shows  this  con- 
dition in  sagittal  section,  Fig.  2  in  cross  section.  If  the  incision  in  the  sac 
is  carried  through  the  internal  ring  into  the  abdominal  cavity,  it  will  be  seen 
that  the  adhesions  of  the  gut  to  the  posterior  surface  of  the  sac  are  continu- 
ous with  the  mesosigmoid,  or  with  the  normal  reflection  of  the  peritoneum 
from  the  bowel  to  the  posterior  abdominal  wall.  An  attempt  to  reduce  the 
bowel  will  be  unsuccessful  until  it  is  separated  from  the  posterior  wall 
of  the  sac  by  sharp  dissection  or  without  reducing  sac  and  gut  together. 
Above  all.  it  is  noteworthy  that  the  adhesions  between  gut  and  sac  wall  show 
no  evidence  of  being  inflammatory,  but  resemble  what  they  really  are,  the 
usual  adhesions  of  the  large  intestine  to  the  posterior  peritoneum  (Fig.  7). 

PATHOGENKSIS. 

In  attempting  to  elucidate  the  various  theories.  1  siiall  speak  principally 
of  adherent  hernia  of  the  sigmoid,  as  what  pertains  to  hernias  of  the  sig- 
moid on  the  left  side  may  be  applied  to  hernias  of  the  caecum  on  the  right. 
I  shall  first  consider  the  commonly  accepted  theory,  that  these  hernias  are 
due  to  the  sliding  of  the  posterior  peritoneum  on  the  underlying  cellular 
tissue,  the  peritoneum  sliding  into  the  internal  ring,  carrying  with  it  the 
attached  loop  of  large  bowel.    This  theory  apjiears  untenalile,  and  rightly  so, 

*  From  tlie  .\nr.als  of  Surgery,  .\ugu>l,    191_'. 
Page  iSO 


/.  LOUIS  RANSOHOFF. 


Figure    1. 

Sagittal    section    of    adherent    hernia 

of    large    intestine,    showing    adhesions 

between    mesentery,    gut    and    posterior 

wall  of  sac. 


Figure  2. 
Cross  section  of  large  intestine,  show- 
ing   adhesions    between    mesentery,    gut 
and    sac    wall,    with    nutrient    vessels    in 
the  adherent  mesentery. 


Cross  section  through  abdomen  at  third  lumbar  vertcljra,  looking  toward  diaphragm, 
showing  mesentery  of  ascending  and  descending  colon  adherent  to  posterior  abdom- 
inal wall. 


as  it  i.s  based  upon  unsound  mechanical  princi])les.  The  iliopelvic  colon  or 
sigmoid  is,  in  pari,  normally  attached  to  the  posterior  peritoneum  at  the 
level  of  the  left  sacro-iliac  synchondrosis,  by  a  broad  fold  of  peritoneum, 
which  appears  deficient  on  the  posterior  aspect  of  the  gut.  That  is,  the 
posterior  surface  of  the  bowel  is  apparently  in  direct  contact  with  the  refo- 
peritoneal  cellular  tissue  of  the  ileopelvic  fossa.  In  a  certain  number  of 
cases,  however,  the  attachment  of  the  ileopelvic  colon  lies  at  a  lower  level 
and  the  anterior  leaf  of  its  peritoneal  covering  is  reflected  to  the  anterior 
abdominal  wall,  just  above  Poupart's  ligament,  the  posterior  leaf  to  the  pos- 
terior abdominal  wall  just  above  the  internal  ring.  This  brings  the  posterior 
uncovered  surface  of  the  bowel  in  direct  contact  with  the  internal  ring,  also 
uncovered  by  peritoneinii,  as  its  peritoneal  covering  has  been  dislocated  to 
the  anterior  abdominal  wall.  .\ny  sudden  increase  in  intra-abdominal  pres- 
sure or  jjrolonged  increase,  as  due  to  straining  at  stool,  is  sufficient  to  force 
the  knuckle  of  bowel  through  the  unprotected  ring  and  into  the  canal.    The 


RANSOHOFF  MEMORIAL  VOLUME 


Figure  4.  Figure  5. 

Figure  4.  Alimentary  tract  of  embryo  of  six  weeks,  showing  rudiiiiciils  of  the 
two  mesenteric  systems  (after  Hertwig). 

Figure  5.  Embryo  of  eight  weeks,  showing  large  intestine  with  free  mesentery 
outlining  the  abdomen. 


r,gur<.  6 
ving  the  adherence  of  the  entire  ascending  and  desccndiny 
ns  beginning  at  the  hepatic  and  splenic  flexures. 


continu.incf  of  presMire  forces  the  gut.  tlraggiiig  the  peritoneum  behind  it, 
furtlier  along  the  canal  into  the  scrotum.  This  low  position  of  the  sigmoid 
is  supposedly  due  to  the  downward  dislocation  of  the  peritoneum  lining  the 
lower  portion  of  the  abdomen.  This  dislocation  is  either  congenital  or  has 
been  caused  by  increased  intra-abdominal  pressure.  It  is  presumed  that  the 
Ijosterior  peritoneum  has  become  loosened  from  its  underlying  supporting 
cellular  tissue.  This  theory,  accepted  by  Ranzi,  Scarpa,  Wier,  Stoney.  and 
many  others,  is  utterly  fallacious.  Even  in  the  opened  abdomen,  it  is  no 
easy  task  to  strip  the  peritoneum  front  the  abdominal  wall,  so  close  is  its 
adherence;  in  addition  to  this,  any  increase  in  intra-abdominal  pressure  only 
serves  to  apply  the  parietal  peritoneum  more  closely  to  the  abdominal  wall. 
If  this  form  of  hernia  occurred  by  sliding  of  the  peritoneum  on  the 
posterior  abdominal  wall,  there  would  be  a  dislocation  of  the  entire  posterior 


/.  LOUIS  RANSOM  OFF. 


peritoneum  \\  ith  the  attached  gut ;  whereas,  the  splenic  flexure  on  the  one 
hand,  and  the  hepatic  flexure  on  the  other,  are  invariably  found  in  their 
normal  antomical  positions.  It  is  true,  that  Tuffier  has  reported  a  case  of 
enormous  hernia  of  the  descending  colon,  where  the  kidney  was  dislocated. 
This,  however,  was  probably  due  to  a  dragging  of  the  inferior  mesenteric 
artery  on  the  aorta  and  the  dislocation  of  the  aorta  and  through  it  a  dislo- 
cation of  th^  kidney.  Again,  if  this  form  of  hernia  occurred  by  sliding, 
there  would  be  from  the  moment  of  occurrence  difficulty  in  reduction; 
whereas,  in  nearly  all  cases  the  history  points  to  the  hernia  having  become 
irreducible  only  after  months  or  even  years. 

Rut  most  convincing  of  all  are  the  few  cases  in  which,  without  visceral 
transposition,  the  Cfecum  has  been  found  adherent  in  left-sided  hernias  and 


Figure  7. 

Oraning    from    life,    slinwiiig    tlie    sigmoid    aillitTcnl    in 

tlie  opened  sac. 

the  sigmoid  in  the  right  hernias.  By  the  utmost  stretch  of  imagination  tiiere 
can  be  no  discussion  on  this  point ;  the  peritoneum  on  the  left  side  cannot 
.slide  into  the  right  inguinal  canal,  nor  vice  versa.  Furthermore,  it  is  almost 
axiomatic  that  the  .f/»r  qua  non  of  the  development  of  a  hernia  of  an  intes- 
tinal coil  is  the  mobility  of  that  coil.  If  a  loop  of  intestine  is  found  fixed  in 
a  hernial  sac.  it  is  conclusive  proof  that  before  the  formation  of  the  hernia 
the  loop  was  mobile.  The  sigmoid  does  not  rest  on  the  cellular  tissue  of  the 
posterior  abdominal  wall,  but  is  separated  from  it  by  a  triplicate  layer  of 
fused  peritoneum.  First  the  posterior  peritoneum  itself,  second  and  third 
the  double  layer  of  adherent  mesentery  through  which  the  nutrient  vessels 
of  the  gut  ])ass  (Fig.  4).  This  same  rclationshi])  exists  between  the  sac 
wall  and  the  adherent  intestinal  coil  (Figs.  1  and  2).  This  fused  peritoneum, 
called  b)-  the  French  the  fascia  d'accolcntcnt,  fixes  the  attached  portion  of 

Fagc    'iS.i 


RAh'SOHOFF  MEMORIAL  VOLUME 


the  sigmoid  and  caecum  firmly  to  the  posterior  abdominal  wall,  and  itself 
prevents  any  possibility  of  sliding  or  dislocation. 

An  ingenious,  though  untenable,  theory  has  been  advanced  by  Lockwood, 
who  claims  that  before  the  descent  of  the  testes  the  right  testicle  lies  in  close 
relationship  to  the  crecum,  the  left  to  the  sigmoid  flexure.  Lockwood  sup- 
])oses  that  an  abnormal  adhesion  develops  between  the  caecum  or  sigmoid 
on  the  one  hand  and  the  right  or  left  testicle  on  the  other.  The  testicle  in 
its  passage  downward  through  the  internal  ring  pulls  on  the  caecum  or  sig- 
moid, as  the  case  may  be,  and  dislocates  it  downward  to  the  region  of  the 
internal  ring,  where  any  slight  increase  in  pressure  is  sufficient  to  force  the 
gut  into  the  inguinal  canal.  The  untenability  of  this  theory  can  be  appre- 
ciated when  it  is  realized  that  the  extraperitoneal  testicle  is  separated  from 


Figure  8. 
Showing  method  of  operating  on  adherent  hernia  of 
sigmoid :   peritoneal   flap  prepared   for  closure  of   ring : 
purse-string    and    continuous   suture    for    formation    of 
new  mesentery  almost  completed. 

tlie  ^'Ut,  not  only  by  the  parietal  peritoneum,  liut  also  bv  the  double  fused 
layer  of  agglutinated  mesocolon.  In  our  many  cases  of  retained  testes,  we 
have  never  encountered  any  such  adhesion.  It  is  just  as  impossible  to  pic- 
ture an  adhesion  occurring  between  the  kidney  and  intestine  as  between  the 
testicle  and  intestine.  However,  even  granting  the  possibility  that  this  adhe- 
sion might  occur,  the  disproportion  in  size  between  the  testicle  and  colon 
would  result  not  in  a  descent  of  the  colon,  but  rather  in  a  retained  testicle. 

Another  theory  almost  too  futile  to  deserve  serious  consideration  has 
been  advanced  by  Savariaud.  He  supposes  that  the  bowel  slips  out  from  its 
mesentery  as  a  glove  finger  is  everted,  passes  behind  the  peritoneum  and  so 
on  into  the  ring.  Considering  that  the  true  length  of  the  colic  mesentery, 
though  adherent,  extends  from  the  vertebral  cuJuinii  to  the  gut.  this  theory 
becomes  immediately  disqualified  (Fig.  ?i). 


/.  LOUIS  RANSOM  OFF. 


It  is  evident  that  none  of  these  hypotheses  can  adequately  or  satisfac- 
torily explain  the  condition  under  consideration.  In  order  to  truly  under- 
stand the  pathogenesis  of  attached  hernias  of  the  large  intestine,  it  is  essen- 
tial to  consider  the  embryology  of  the  intestinal  tract,  its  mesenteries,  and 
particularly  the  secondary  changes  in  the  mesentery  of  the  large  intestine. 

During  the  fourth  week  of  embryonic  life,  the  alimentary  tract  stretches 
as  a  straight  tube  from  primitive  mouth  to  anus.  All  but  the  upper  portion 
is  attached  behind  to  the  chorda  by  a  straight  double  mesentery,  the  layers 
of  which  enclose  at  the  base  the  primitive  aorta.  The  first  differentiation 
of  this  tube  into  its  separate  parts  begins  with  the  development  of  a  small 
spindle-shaped  enlargement,  the  stomach.  The  rest  of  the  alimentar)-  tube 
is  still  connected  with  the  yolk  sac.  The  further  alteration  in  the  shape  and 
position  of  the  alimentary  tube  and  its  mesenteries  is  due  to  the  dispropor- 
tionate lengthening  of  the  tube,  that  is,  disproportionate  to  the  development 
of  the  abdominal  cavity.  Consequently,  to  find  room,  the  intestinal  canal 
must  take  a  winding  and  tortuous  course. 

The  stomach  is  the  first  portion  of  the  intestinal  tract  to  begin  its  axial 
rotation,  turning  so  that  the  left  side  becomes  the  anterior  surface  and  lesser 
curvature,  the  right  side  the  posterior  surface  and  greater  curvature.  This 
brings  the  pylorus  slightly  to  the  right  of  the  median  line,  and  begins  the 
twisting  of  the  intestine.  The  twisting  of  the  small  intestine  takes  place 
about  the  origin  of  the  superior  mesenteric  artery,  and  both  it  and  the  large 
intestine  rotate  in  the  direction  opposite  to  that  of  the  hands  of  a  clock. 

In  an  embryo  of  six  weeks  the  intestinal  tract,  greatly  increased  in  length, 
has  already  formed  two  distinct  loops  both  running  in  an  anteroposterior 
direction.  In  these  loops  can  be  recognized  the  rudiments  of  the  two  mes- 
enteric systems,  the  great  or  superior  and  the  lesser  or  inferior  (Fig.  4). 
From  the  pylorus  the  intestinal  tube  runs  directly  backward  to  the  verte- 
bral column ;  from  here  a  sharp  bend  downward  and  forward  toward  the 
umbilicus ;  from  the  umbilicus  back  to  the  vertebral  column  and  then 
straight  on  to  the  rectum.  The  U])per  loop  consists  of  two  nearly  parallel 
arms  connected  to  the  vertebral  column  by  a  sagittal  mesenterv.  in  which 
runs  the  first  evidence  of  the  superior  mesenteric  artery.  At  the  apex  of  the 
loop  is  the  now  occluded  viteline  duct.  A  little  further  toward  the  caudal 
end  of  the  embryo  is  found  a  slight  enlargement,  the  beginning  of  the  large 
intestine.  At  this  stage  the  lesser  or  inferior  mesenteric  system  can  also  be 
distinguished  near  the  caudal  end  of  the  embryo.  During  the  third  month 
further  changes  occur  in  the  size  and  position  of  the  stomach.  As  these 
changes,  however,  are  not  germane  to  the  subject  under  consideration,  it 
suffices  to  say  that  the  twisting  of  the  stomach  and  its  mesentery  results  in 
the  formation  of  the  bursa  omentalis.  The  changes  in  the  small  and  large 
intestine,  particularly  the  variations  in  the  relation  of  their  mesenteries,  are 
of  paramount  importance  to  the  comprcliensive  ex]:)osition  of  hernias  of  the 
large  intestine.  The  duodenum  is  the  only  [xjrtion  of  the  small  intestine  which 


RAXSOHOFF  MEMORIAL  VOLUME 


retains  its  early  embryonic  position.  It  is  attached  to  the  vertebral  cokimn 
bv  a  short  mesentery,  which  early  fuses  with  the  parietal  peritoneiun,  thus 
])ernianently  fixing  the  duodenum  in  place. 

The  increase  in  length  of  small  intestine  is  accomniodated  by  the  folding 
of  its  mesentery  in  a  frill  shape,  the  base  narrow  and  the  outer  edge  of  great 
length.  The  most  important  change,  however,  takes  place  in  the  position  of 
the  large  intestine  and  its  mesentery.  This  fact  must  always  be  borne  in 
mind :  the  large  intestine  at  all  times  possesses  a  long  mesentery  and  is  at  no 
^tage  or  in  no  part  extraperitoneal  (Fig.  3).  The  caecum  is  at  this  stage 
rotated  across  the  abdomen  from  below  upward  and  from  right  to  left  and 
again  to  the  right,  until  it  occupies  a  position  under  the  liver.  This  ascend- 
ing loop,  which  later  forms  the  entire  large  intestine,  thus  crosses  the  loop 
of  small  intestine  from  below  upward  and  from  right  to  left,  crossing  at  the 
duodenum,  carrying  its  mesentery  with  it.  This  explains  why  the  duodenum 
is  buried  under  the  transverse  mesocolon  (Fig.  5).  The  cjecum,  in  the 
adult  sense  of  the  word,  is  not  yet  developed,  as  it  is  not  an  integral  part  of 
the  embryonic  large  intestine,  but  a  pouching  or  evagination  of  its  wall. 
The  transverse  colon  as  in  adult  life  crosses  the  duodenum  to  jhe  splenic 
flexure  and  from  there  on  the  descending  colon  to  the  rectum.  In  later 
embryonic  life  the  ca?cum  descends  toward  the  right  pelvis,  forming  the 
ascending  colon. 

This  description  has  been  undertaken  to  show  that  the  entire  large  intes- 
tine has  a  distinct  mesentery  and  lies  free  in  the  abdominal  cavity.  The  large 
intestine  forms  a  horseshoe,  outlining  the  confines  of  the  peritoneal  cavity. 
Grouped  in  the  center  are  the  small  intestines  (Fig.  5).  The  secondary 
adhesions,  which  now  form,  change  the  mobile  fetal  large  intestine  into  the 
fixed  adult  type. 

Peritoneal  surfaces  have  a  tendency  to  adhere  when  they  are  held  in  con- 
tact under  pressure.  The  small  intestine,  and  particularly  its  mesentery,  does 
not  adhere  to  the  parietal  peritoneum,  for  two  reasons :  (1)  From  the  time 
of  the  development  of  the  liver  in  the  fifth  week,  the  small  intestines  are 
filled  with  its  secretion,  and  in  a  state  of  active  peristalsis;  (2)  its  frilled 
mesentery  presents  no  broad  surface  for  agglutination. 

The  conditions  in  the  large  intestine  and  its  mesentery  are  the  reverse. 

(1)  The  broad  flat  mesentery  stretching  on  either  side  from  the  verte- 
bral column  to  the  large  gut  rests  directly  on  the  posterior  parietal  peri- 
toneum (Fig.  4).  Moreover  as  the  large  bowel  is  empty  and  not  in  active 
peristalsis,  it  is  immobile. 

(2)  The  mesentery  is  held  in  contact  to  the  posterior  parietal  peri- 
toneum not  only  by  the  pressure  of  the  filled  moving  small  intestines,  but 
also  by  intra-abdominal  pressure. 

(3)  Still  another  feature  is  the  increase  in  local  pressure  at  the  site  of 
the  projecting  kidneys  and  adrenals,  which  force  the  parietal  peritoneum  in 
direct  contact  with  the  ascending  and  descending  colon. 


Page  ise 


J.  LOUIS  RANSOHOFF. 


The  adhesion  of  mesentery  always  ])recedes  the  adhesion  of  the  bowel ; 
that  is,  the  adhesions  begin  at  the  root  of  the  mesenteries  and  spread  toward 
bowel.  Failure  of  the  adhesions  to  be  continuous  results  in  tlie  ileocrecal 
fossa  on  the  right  side,  the  parasigmoid  on  the  left  (Fig.  3). 

The  agglutination  of  the  large  intestine  begins  at  the  transverse  meso- 
colon, which  adheres  to  the  great  bursa.  The  transverse  colon,  however, 
retains  its  mobility  by  the  mobolity  of  the  bursa  itself.  According  to  Brow- 
man,  the  limits  of  adherence  of  the  ascending  and  descending  colons  depend 
entirely  on  the  retroperitoneal  position  of  the  kidney  and  adrenals.  Only 
those  portions  of  the  colon  lying  directly  on  the  anterior  surface  of  the  kid- 
ney and  adrenals  adhere,  which  accounts  for  the  comparative  mobility  of 
the  caecum  and  ileopelvic  colon,  both  of  which  lie  below  the  level  of  the 
kidney.  This  explanation  of  the  mobility  of  the  cascum  and  pelvic  colon, 
while  very  plausible,  does  not  explain  those  cases  in  which  the  entire  descend- 
ing and  ileopelvic  colon  is  found  adherent  to  the  posterior  peritoneal  wall 
(Fig.  6).  The  theory,  which  seems  more  plausible,  is  that  advanced  by 
Lardennois.  that  the  secondary  adhesions  of  the  large  intestine  begin  at  two 
points:  on  the  right  side  at  the  hepatic  flexure,  at  the  entrance  into  the 
mesentery  of  the  highest  branch  of  the  right  colic  branch  of  the  superior 
mesenteric  artery  (Fig.  6)  ;  on  the  left  side  at  the  splenic  flexure,  where  the 
highest  branch  of  the  inferior  mesenteric  artery  first  enters  the  descending 
mesocolon,  this  adhesion  being  continuous  with  the  phrenocolic  ligament. 
It  is  interesting  to  state  here  that  no  matter  how  great  the  ptosis  or  disloca- 
cation  of  the  colon,  the  hepatic  and  splenic  flexures  are  invariably  found  in 
their  fixed  positions.  Beginning  at  the  hepatic  flexures  on  the  right  side  the 
mesentery  of  the  ascending  colon  adheres  along  its  entire  length,  the  adhe- 
sions increasing  in  extent  as  the  head  of  the  colon  descends.  The  adhesions 
begin  at  the  inner  border  of  the  mesentery  and  spread  toward  the  peri- 
])hery.  The  cjecum  being  a  pouching  of  the  head  of  the  large  bowel  has 
no  mesentery  and,  therefore,  does  not  adhere.  The  extent  of  mobility  of 
the  caecum  depends  entirely  on  its  length  ;  a  short  caecum  being  only  slightly 
mobile  will  never  be  found  in  a  hernial  sac,  while  a  long,  freely  movable 
cascum  has  almost  the  same  opportunity  of  entering  the  hernial  sac  as  a  coil 
of  small  intestine.  This  comparative  mobility  of  the  caecum  is  often  observed 
during  operation  in  the  appendix  region.  Every  operator  realizes  how  sim- 
ple it  is  in  some  cases  to  deliver  the  cascum  through  a  gridiron  incision  and 
how  difticult  in  others.  The  adhesion  of  the  descending  colon  begins  at  the 
splenic  flexure  and  passes  progressively  downward  along  the  whole  course 
of  the  posterior  abdominal  wall  to  the  brim  of  the  pelvis. 

It  is  necessary  at  this  point  to  consider  the  measurements  of  the  dift'erent 
parts  of  the  colon.  The  left  colon  is  arbitrarily  divided  into  the  descending 
and  ileopelvic  portions.  The  length  of  the  descending  colon  is  fairly  con- 
stant, measuring  about  14  cm.  The  ileopelvic  portion  on  the  other  hand 
varies  within  the  enormous  limits  of   14-81  cm.     Evidently  the  longer  the 

Page  I,H1 


RAXSOHOFF  MEMORIAL  VOLUME 


colon  the  greater  will  be  its  mobility,  as  only  that  portion  will  adhere  which 
comes  into  direct  contact  with  the  ])Osterior  jieritoneuni.  An  extremely  long 
ileopelvic  colon  partakes  of  the  nature  of  the  small  intestine,  and  for  this 
reason  has  the  same  chance  of  entering  the  hernial  sac.  A  short  colon 
stretched  from  the  splenic  flexure  to  the  rectum  would  be  adherent  along 
its  entire  length  (Fig.  6),  and  this  brings  out  the  crucial  point,  it  could  not 
[jossibly  become  engaged  in  a  hernia. 

What  is  the  cause  of  the  adherence  of  the  large  intestine,  when  it  finally 
gains  access  to  the  hernial  sac?  Its  early  reducibility  is  sufficient  proof, 
that  in  the  beginning  it  is  nonadherent.  The  reason  for  its  adherence  is  that 
under  resumed  embryonal  conditions  it  follows  its  embryonal  tendencies.  In 
the  hernial  sac,  the  broad  flat  mesentery  of  the  large  intestine  comes  into 
direct  contact  with  the  peritoneal  surface  of  the  sac.  Moreover,  the  two  peri- 
toneal surfaces  are  held  in  contact  under  considerable  pressure,  as  the  large 
intestine,  particularly  by  pelvic  colon,  is  usually  distended  with  faeces.  Be- 
side, the  large  intestine,  unlike  the  small  intestine,  is  comparatively  immobile 
and  seldom  in  a  state  of  active  peristalsis.  Thus  we  have  the  requisites  for 
peritoneal  agglutination  present:  (1)  Broad  flat  surfaces  held  in  contact 
under  pressure;   (2)  comparative  immobility. 

As  in  embryonic  life,  the  adhesions  begin  behind,  at  the  attachment  of  the 
mesentery,  and  progress  steadily  around  the  sac  (Figs.  1,  2,  and  7).  There 
are  cases  reported  of  so-called  hernias  without  sacs,  where  the  entire  sac  has 
been  obliterated  by  these  adhesions. 

To  recapitulate:  After  studying  the  embryology  of  the  large  intestine 
and  the  secondary  adhesions  of  its  mesenteries,  the  following  conclusions 
may  safely  be  drawn : 

1.  So-called  hernias  with  incomjilelc  sacs  do  not  exist,  except  as  a  sec- 
ondary process. 

2.  The  sac  is  complete  in  its  incipiency  and  has  been  obliterated  by 
secondary  adhesions  of  the  embryonal  type. 

3.  A  loop  of  intestine  found  in  a  hernial  sac  is  conclusive  i)roof  that 
originally  that  loop  was  mobile. 

4.  hi  adherent  hernias  of  the  large  intestine  the  hernia  is  i)rimary.  the 
adhesions  secondary. 

5.  The  crux  of  the  situation  is  the  redundant  colonic  loop. 
Morphologically,  three  forms  of  hernia  of  the  large  intestine  may  be  dis- 
tinguished, the  varieties  based  on  the  relationship  of  contents  to  sac: 

1.  The  sac  is  complete.  That  is.  there  are  no  adhesions  between  the  sac 
wall  and  gut.  This  form  differs  in  no  wise  from  the  ordinary  reducible 
hernias  of  the  small  intestine.  The  loop  of  the  bowel  and  its  mesentery  are 
easily  reduced.  This  form  of  hernia  occurs  when  from  an  early  stage  in  its 
existence  the  hernia  has  been  kept  in  jilace  by  a  truss,  and  no  chance  has 
been  given  for  the  formation  of  adhesions. 

2.  The  most  common  form  of  hernia  of  the  large  intestine  is  that  with 
l)artial  obliteration  of  the  sac  by  secondary  adhesions,  tlie  SD-called  hernia 


/.  LOUIS  RANSOM  OFF. 


with  incomplete  sac  (Figs.  1.  2,  and  7).  The  posterior  portion  of  the  sac 
has  become  obhterated  by  adhesions  beginning  at  the  mesentery  behind  and 
extending  to  a  variable  distance  around  the  sac.  The  entire  loop  of  bowel 
is  usually  found  adherent,  beginning  below  at  the  base  of  the  sac  and  extend- 
ing to  the  neck.  When  the  cjECum  and  appendix  are  engaged  in  a  hernia, 
the  adhesion  begins  at  the  broad  flat  mesentery  of  the  head  of  the  colon  and 
the  first  loop  of  the  ileum. 

3.  Hernia  with  complete  obliteration  of  the  sac,  the  so-called  sacless 
hernia,  is  extremely  rare  and  very  few  cases  have  been  reported,  '{'here  is 
.some  doubt  whether  this  form  of  hernia  really  exists,  and  whether  some 
portion  of  the  sac,  however  small,  is  not  always  preserved. 

These  adherent  hernias  of  the  large  intestine  are  seldom  strangulated, 
probably  due  to  the  large  size  of  the  ring,  which  has  been  enlarged  by  the 
thick-walled  large  bowel  and  its  semi-solid  contents.  On  the  other  hand, 
inflammation  and  the  presence  of  fibrinous  exudates  in  the  sac  are  not  of 
unusual  occurrence,  as  in  Case  I.  This  is  perhaps  due  to  an  injury  of  the 
irreducible  gut,  and  the  migration  through  its  wall  of  bacteria. 

On  opening  the  sac  by  a  hernia-laparotomy  incision,  it  is  found  that  the 
adhesions  of  the  gut  to  the  posterior  surface  of  the  sac  are  continuous  with 
the  mesosigmoid,  or  with  the  normal  reflexion  of  the  peritoneum  to  the 
posterior  abdominal  wall.  The  gut  is  continuous  with  the  pelvic  colon  or 
with  the  ascending  colon  as  the  case  may  be.  The  adhesions  are  so  dense 
that  it  seems  as  though  the  sac  is  really  deficient  behind.  What  is  most 
important  is  the  fact  that  the  nutrient  vessels  of  the  bowel  are  found  in  the 
adhesions.  An  attempt  to  separate  these  adhesions  by  blunt  dissection  is 
unsuccessful.  The  anterior  part  of  the  sac  is  free,  the  posterior  wall  is 
formed  by  the  loop  of  gut,  which  seems  to  be  really  incorporated  in  the  wall 
of  the  sac,  the  peritoneum  of  the  sac  appearing  to  be  continuous  with  the 
covering  of  the  bowel  (Fig.  7).  There  are  frequently  other  contents  of 
these  hernial  sacs.  On  the  right  side  the  first  coil  of  ileum  with  its  mesen- 
tery may  be  found  adherent  in  the  sac,  on  the  right  or  left  side  free  coils  of 
small  intestine.  Unless  strangulated,  the  small  bowel  is  easily  reduced,  leav- 
ing the  hernial  sac  with  the  large  bowel  attached  to  its  wall.  In  some  in- 
stances the  adhesions  may  be  so  dense  as  to  include  the  extraperitoneal  testi- 
cle and  cord.  Cases  have  been  reported  in  which  the  testicle  was  so  adher- 
ent that  it  was  necessary  to  sacrifice  it  before  radically  curing  the  hernia. 
This,  however,  seems  in  the  majority  of  cases  unjustifiable. 

Symptomatology. — Though  the  symptoms  of  these  hernias  are  not  in  any 
way  distinctive,  there  are  certain  suggestive  features  which  point  to  the  pos- 
sibility of  a  diagnosis  being  made.  Usually  occurring  in  males,  these  hernias 
come  on  after  adult  life.  At  first  reducible,  they  become  irreducible  after 
months  or  sometimes  years.  If  sigmoid  hernias,  they  have  a  doughy  feeling 
and  cause  their  bearer  less  discomfort  after  a  thorough  evacuation  of  the 
bowels.  If  a  hernia  of  this  sort  is  suspected,  the  diagnosis  could  easily  be 
made  by  the  injection  of  bismuth  per  rectum,  followed  by  a  radiogram.     It 


RANSOHOPF  MEMORIAL  VOLUME 


is  during  operation  that  the  diagnosis  can  and  must  be  made,  as  only  by  pre- 
cisely understanding  the  condition  present  can  proper  treatment  be  insti- 
tuted. After  exposure  and  isolation  of  the  sac  in  a  radical  herniotomy,  it 
is  the  practice  of  many  surgeons  to  attempt  to  reduce  the  contents  before 
opening  the  sac.  If  this  maneuvre  is  unsuccessful,  an  immediate  suspicion 
of  adherent  hernia  should  be  roused,  and  the  greatest  precautions  taken  to 
obviate  injury  to  the  bowel.  The  sac  should  be  palpated  with  the  gloved 
finger  and  a  non-adherent  portion  found,  which  is  invariably  in  the  anterior 
portion  of  the  sac.  Grasping  this  non-adherent  portion  of  the  sac  with 
forceps,  it  is  lifted  free  from  the  underlying  contents  and  opened  by  a  .small 
incision.  The  opening  is  enlarged  upward  toward  the  neck  of  the  sac  pre- 
ceding the  incision,  with  the  finger  or  grooved  director.  In  extending  the 
opening  of  the  sac  downward,  it  is  well  to  exert  great  care  not  to  injure  the 
cross  loop  of  the  bowel.  After  freely  opening  the  sac,  if  this  form  of  hernia 
is  borne  in  mind,  the  diagnosis  can  surely  be  made.  If  a  gentle  attempt  is 
made  to  separate  these  adhesions,  it  will  be  found  unsuccessful  without  using 
undue  force.  In  fact  any  attempt  to  separate  these  adhesions  is  unjustifiable 
and  may  result  in  disaster. 

Treatment. — According  to  Weir,  Heydenreich  attempted  this  manoeuvre 
in  two  cases,  both  followed  by  fecal  fistula  and  recurrence  of  the  hernia. 
Numerous  like  disasters  have  been  reported.  Fearing  a  similar  result, 
Jaboulay  resected  the  entire  adherent  loop  of  bowel. 

No  matter  what  method  of  treatment  is  followed,  it  is  essential  that  the 
neck  of  the  sac  should  be  well  exposed.  To  accomplish  this  exposure,  it  is 
frequently  necessary  to  perform  a  hernia-laparotomy.  This  is  done  by  intro- 
ducing the  finger  through  the  internal  ring  and  cutting  the  internal  oblique 
to  a  variable  extent  above  the  ring.  After  this  is  done,  one  of  several  meth- 
ods of  treatment  may  be  instituted.  Savariaud's  method  is  in  fact  a  reduc- 
tion of  the  sac  and  bowel  en  masse.  This  method  was  practiced  in  Cases  I 
and  II.  In  order  to  thoroughly  complete  this  operation,  the  sac  and  its  con- 
tents must  be  well  exposed  above  the  internal  ring,  which  must  be  stretched 
sufficiently  wide  to  permit  the  passage  of  the  sac  and  its  contents  without 
using  undue  force.  In  his  original  description  of  the  operation,  Savariaud 
advised  the  closure  of  the  incision  in  the  sac  wall  before  reduction  is  at- 
tempted. The  sac  and  its  contents  are  then  forced  through  the  internal  ring 
as  though  inverting  a  gloved  finger.  The  ring  is  closed  by  bringing  the 
edges  of  the  inverted  sac  in  apposition  by  interrupted  sutures.  The  operation 
is  completed  as  an  ordinary  herniotomy. 

The  disadvantages  of  this  operation  are  the  insecurity  of  the  closure  of 
the  ring  and  the  danger  which  always  attends  the  reduction  of  a  hernia  en 
masse.  That  is,  there  is  a  possibility  of  later  strangulation  within  the  reduced 
.sac.  The  operative  procedure  followed  in  Case  III,  which  is  a  slight  modi- 
fication of  a  method  described  by  Hotchkiss  in  1910,  seems  to  offer  greater 
advantages  in  that  it  results  in  a  return  to  fairly  normal  anatomical  relations. 
After  division  and  thorough  exposure  of  the  sac  (Fig.  7)  it  will,  as  a  rule. 

Page  i90 


/.  LOUIS  RANSOHOFP. 

be  seen  that  one  side  of  the  sac  is  of  greater  width  than  the  other.  In  this 
event  the  more  ample  peritoneal  surface  is  chosen  as  a  flap  to  cover  tiie  ring. 
In  case  the  peritoneal  surfaces  are  of  almost  equal  extent  the  mesial  portion 
of  the  sac  should  be  utilized  for  this  purpose. 

The  portion  of  the  sac  chosen  as  a  covering  for  the  ring  is  separated  by 
an  incision  beginning  at  the  bottom  of  the  sac  and  running  parallel  to  and 
at  least  one  inch  from  the  gut  wall.  The  flap  is  completely  freed  below,  left 
attached  above  to  the  peritoneum  covering  the  internal  aspect  of  the  ring 
(Fig.  8).  The  loop  of  bowel  is  now  pulled  out  well  through  the  ring  and 
reflected  on  the  abdomen.  The  attached  flaps  of  the  sac  are  now  united  on 
the  posterior  surface  of  the  bowel  by  a  fine  running  catgut  suture,  thus  form- 
ing a  new  mesocolon.  The  suture  is  begun  above  at  the  cross  loop  of  the 
bowel  by  using  a  wide  purse-string  suture  so  as  to  prevent  angulation. 
After  the  continuous  suture  is  completed,  the  loop  of  bowel  is  easily  reduced. 
The  ring  is  closed  by  suturing  the  prepared  flap  of  peritoneum  to  the  peri- 
toneum covering  the  internal  ring.  The  margins  of  the  internal  oblique,  if 
divided,  are  exactly  approximated,  and  the  operation  completed  after  the 
Bassini  method.  Lardonnois  and  Okinji  suggested  that  as  these  hernias  are 
due  to  the  mobility  of  the  large  intestine,  they  should  be  treated  by  fixing 
the  intestine  to  the  posterior  peritoneal  wall.  After  exposing  the  sac,  the 
neck  is  well  exposed  by  a  hernia-laparotomy  and  the  gut  carefully  dis- 
sected from  the  sac.  The  loop  of  large  intestine  is  then  sutured  as  high  as 
possible  to  the  posterior  peritoneal  wall  as  in  colopexy.  In  extreme  cases 
it  might  be  well  to  combine  this  procedure  with  the  method  of  operation 
described  above.  In  a  class  of  cases  presenting  so  many  difficulties,  prob- 
ably no  one  method  of  treatment  will  be  applicable  to  all  cases,  and  a  combi- 
nation of  two  methods  may  occasionally  be  of  advantage. 

The  following  cases  are  from  the  records  of  Dr.  Joseph  RansohofT  and 
the  writer : 

Case  I.  U.  L.,  aged  54.  Complained  of  left  inguinal  hernia,  which  had 
been  present  for  many  years,  but  had  only  become  irreducible  during  ])ast 
two  years.  Examination  revealed  a  left  irreducible  inguinal  hernia,  the  size 
of  an  orange. 

Operation  (Jewish  Hospital,  March  7,  1908).  Cas-ether  anesthesia. 
After  opening  the  sac  the  descending  colon  was  found  adherent  to  its  pos- 
terior wall.  The  gut  and  sac  were  reduced  en  masse,  and  the  ring  closed 
by  suture.  The  operation  was  completed  as  a  typical  Bassini.  The  recov- 
ery was  uncomplicated  and  there  has  been  no  recurrence. 

Case  If.  A.  L.,  aged  53.  Had  had  a  hernia  for  two  years,  which  became 
irreducible  during  the  last  two  months.  During  past  two  days  the  hernia 
was  swollen,  tender  and  painful.  Examination  revealed  a, tense  irreducible 
left  inguinal  hernia,  the  size  of  two  fists. 

Operation  (Jewish  Hospital,  May  13,  1909).  Gas-ether  anesthesia. 
After  exposing  the  sac  in  the  usual  way,  incision  into  it  revealed  the  in- 
flamed and  thickened  sigmoid  loop  adherent  to  the  posterior  wall  of  the  fac. 


RANSOM  OFF  MEMORIAL  VOLUME 


Gut  and  sac  were  reduced  en  masse  and  the  ring  closed  by  the  suture  of 
the  inverted  sac  wall.  The  operation  was  completed  as  a  typical  Bassini. 
Recovery  was  uneventful,  and  there  has  been  no  recurrence. 

Case  III.  D.  B.,  aged  59.  Had  an  irreducible  inguinal  hernia,  which 
had  been  present  for  twenty  years.  During  past  three  years  hernia  had 
become  irreducible.  Examination  revealed  a  \ery  corpulent  man  with  a 
large,  irreducible,  left  inguinal  hernia. 

Operation  (Jewish  Hospital,  July  29,  1911).  Gas-o.xygen-ether  anes- 
thesia. After  exposing  the  sac  in  the  usual  way,  an  attempt  to  reduce  its 
contents  before  opening  was  unsuccessful.  On  opening  the  anterior  part  of 
the  sac,  a  loop  of  the  sigmoid  about  ten  inches  long  was  found  adherent  to 
its  posterior  wall.  The  neck  of  the  sac  was  exposed  by  incising  the  internal 
oblique.  A  peritoneal  flap  for  the  closure  of  the  ring  was  made  as  described 
above.  The  two  attached  portions  of  the  sac  were  united  over  the  posterior 
surface  of  the  gut  by  a  running  catgut  suture.  The  gut  with  its  new  formed 
mesentery  was  easily  reduced  and  the  ring  closed  by  suturing  the  prepared 
flap  to  the  margins  of  the  ring  by  interrupted  catgut  sutures.  After  care- 
fully approximating  the  cut  margins  of  the  internal  oblique,  the  operation 
was  completed  as  a  typical  Bassini.  Recovery  was  uneventful,  and  there 
has  been  no  recurrence. 


THE  DANGERS  AND  FALLACIES   OF  INTRASPINOUS 
INJECTION  OF  SALYARSAN.* 

William  Ravink.  M.  D. 

Cincinnati. 

In  our  zeal  to  combat  syphilis  of  the  central  nervous  system,  we  are 
prompted  more  by  enthusiasm  and  theory  than  by  reason  and  judgment. 
Time-honored  weapons,  which  have  served  us  well  in  our  therapeutic  amia- 
mentarium.  are  cast  aside,   to  join   the  ever-growing  number  of   faddists. 

The  Direct  Intradural  Injection  of  Salvarsan. — Wechselman,  in  1912, 
and  Alarinesco.  in  1913,  reported  unsuccessful  attempts  at  the  direct  intra- 
dural injections  of  salvarsan.  Ravaut,  however,  reports  some  favorable 
results  from  this  method.  A\'ile  expresses  confidence  in  the  method  of  Ra- 
vaut, but  ]ioints  out  the  dangers  of  its  use ;  where  there  are  any  involvement 
of  bladder  and  rectum,  these  constitute  for  him  a  decided  contra-indication. 
Gordon  reports  a  most  disastrous  case  following  the  intradural  injection 
of  neosalvarsan,  after  the  method  and  technique  of  Ravaut,  a  synopsis  of  the 
case  which  I  will  quote :  "The  patient,  a  man  of  thirty-five  years  of  age, 
presented  all  the  typical  symptoms  of  tabes  dorsalis.  At  the  time  he  came 
under  my  observation,  pain  in  the  lower  extrenieties,  ataxia,  incontinence 
of  urine  and  constipation  were  the  most  conspicuous  manifestations.  For- 
merly. I  was  told,  he  had  the  usual  course  of  treatment  with  iodids  and 
mercury.  At  this  time  the  Wasserniann  reaction  of  serum  and  spinal  fluid 
was  positive.  I  proposed  at  once  the  treatment  with  auto-salvarsanizcd 
serum,  which  was  promptly  accepted.  The  result  from  one  injection  was 
gratifying.  The  pain  had  almost  disappeared,  the  ataxia  improved,  also 
the  incontinence  of  urine  decreased  considerably.  Constipation  remained 
unaltered. 

"For  a  period  of  two  months  the  patient  felt  very  comfortable.  Soon, 
however,  the  bladder  disturbance  returned.  As  the  Wasserniann  reaction 
was  at  this  time  positive,  the  patient  finally  accepted  the  ofifer  to  have  an- 
other intraspinal  injection,  which  he  had  repeatedly  refused  during  the 
past  two  months.  With  the  patient's  consent,  I  had  recourse  this  time  to  the 
direct  intradural  injection  of  neosalvarsan  instead  of  the  salvarsanized 
serum.  Accordingly  I  had  the  fluid  prepared  after  Ravaut's  technique.  The 
solution  used  was  a  6  per  cent,  neosalvarsan  in  distilled  water.  As  each  drop 
of  the  solution  contained  three  mg.  of  neosalvarsan,  only  two  drops  were 
injected  from  a  specially  constructed  and  very  accurately  graduated  syringe. 
The  lumbar  puncture  was  made  with  a  needle,  the  end  of  which  fitted  the 
graduated  syringe.  After  a  small  quantity  of  spinal  fluid  had  flowed  out 
of  the  cannula  and  been  collected  in  a  tube  for  diagnostic  purposes,  the 
syringe  was  attached  and  the  fluid  was  allowed  to  run  in.  in  order  to  mix 

*  Read   before    the    Academy    of    Medicine,    of    Cincinnati.    January    IS,    19Lv— From    The    Lancet- 


RANSOHOFF  MEMORIAL  VOLUME 


with  the  drug.  Then  the  mixed  fluid  was  pushed  gently  into  the  canal. 
The  ]irocedure  of  mixing  was  repeated  the  second  time.  The  patient  was 
then  placed  in  the  Trendelenburg  position.  One  half-hour  after  the  injection 
the  patient  commenced  to  complain  of  severe  pains  in  the  lower  limbs,  which 
in  subsequent  days  became  more  and  more  pronounced.  Vomiting  appeared 
on  Ibe  same  day  and  kept  uj)  for  six  consecutive  days.  Retention  of  urine 
took  the  place  of  the  former  incontinence.  Incontinence  of  feces  made  its 
appearance.  All  these  symptoms  continued  without  relief.  On  the  fifth 
day.  small  erythematous  patches  appeared  on  the  glans  penis,  scrotum  and 
the  sacrum.  They  gradually  became  larger  and  finally  distinctly  gangrenous. 
Two  weeks  after  the  injection  the  patient  presented  the  following  picture: 
He  was  unable  to  stand  or  walk;  he  suffered  agonizing  pains  in  the  lower 
limbs,  so  that  sleep  was  impossible ;  retention  of  urine  and  incontinence 
of  feces  were  exceedingly  disturbing;  the  gangrene  of  the  above-mentioned 
areas  was  becoming  more  and  more  profound ;  the  temperature  reached 
102  to  103°  F. ;  he  vomited  daily,  lost  his  appetite  and  was  losing  weight, 
r.radually  the  condition  grew  more  and  more  alarming  and  finally  he  ex- 
pired. This  case  seems  to  militate  against  the  direct  intradural  injection 
of  neosalvarsan,  notwithstanding  the  favorable  reports  of  Ravaut  and  Wile. 
.\nimal  cx])erimentation  with  the  direct  intradural  injection  of  salvarsan 
in  monkeys  had  to  be  abandoned  on  account  of  the  caustic  and  destructive 
action  of  the  drug. 

"Tile  direct  intradural  injection  has  now  been  for  the  greater  part 
supp'anlcd  by  the  ingenious  method  of  the  salvarsanized  serum  injection 
of  Swift-Ellis,  for  the  technique  of  which  the  reader  is  referred  to  the 
original  article.  One  thing  which  all  the  writers  who  laud  this  method  over 
all  others  forget  to  mention  is  this:  The  main  reliance  of  tlie  Swift-Ellis 
method  lies  in  the  intravenous  injection  of  salvarsan  preceding  the  intra- 
spinous  injection,  a  point  which  the  originators  of  the  method  personally 
mentioned  and  emphasized  to  the  writer,  and  quoting  verbatim  from  their 
original  article  the  following:  'In  dealing  with  syphilis  of  the  central  nervous 
system,  we  are,  however,  more  fortunate  than  is  the  case  in  purulent  men- 
ingitis, for  here  the  introduction  of  our  therapeutic  agents  into  the  general 
circulation  is  of  undoubted  benefit.  With  mercury,  iodids  and  with  salvarsan 
intravenously,  much  can  be  done,  and  in  many  patients  all  clinical  signs  and 
symptoms  can  be  relieved.'  " 

What  is  accomplished  by  the  Swift-Ellis  method  of  treatment?  Wasser- 
mann  plus  is  changed  to  negative.  The  number  of  lymphocytes  in  the  cere- 
bro-spinal  fluid  is  reduced.  Globulin  reaction  becomes  negative.  In  other 
words,  the  improvement  shown  is  a  biochemical  or  laboratory  improve- 
ment. The  high  cell  count  and  the  globulin  reactions  are  the  manifestations 
of  an  inflammatory  process,  and  it  is  questionable  whether  its  reduction 
is  going  to  be  a  distinct  advantage  to  the  patient ;  we  must  not  lose  sight 
of  bis  general  condition.    Clinically,  no  results  are  reported  aside  from  the 


WILLIAM  RAVINE 


fact  that  the  patients  are  reported  as  feeling  better.  Wiiat  a  variable  quan- 
tity this  is. 

This  method  is  not  without  its  dangers,  as  we  are  but  to  refer  to  the 
fatalities  which  occurred  at  Los  Angeles  in  seven  cases  after  the  intraspinous 
injection  of  salvarsanized  serum.  The  method  is  more  painful,  requiring 
very  often  opiates  for  the  relief  of  pain  in  the  legs.  Paralyses  of  the  legs. 
incontinence  of  urine  and  feces  persisting  for  months,  and  later  followed 
by  death. 

Sachs  reports  a  case  of  paresis  developing  an  acute  ascending  paralysis  of 
Landry  after  the  sixth  intraspinous  injection,  all  of  the  injections  having 
been  tolerated  with  great  comfort. 

Myerson  reports  several  cases  which  grew  rapidly  worse  after  this 
method.    One  case  in  particular  merits  its  rei)roduction  here. 

Case  No.  11737. — F.  M.  L.,  male,  aged  thirty-nine  years,  married;  en- 
tered May  6,  1913.  The  occasion  of  the  patient's  commitment  was  the  sud- 
den maniacal  outbreak  in  the  house  of  a  friend.  Family  history,  negative. 
Had  a  high  school  education.  He  had  been  a  spendthrift,  a  heavy  drinker, 
and  led  a  dissolute  life.  At  first  he  denied  syphilis,  but  later  admitted  having 
it  years  ago.  At  the  time  of  entrance  he  was  clearly  oriented.  Memory 
seemed  intact ;  no  hallucinations  or  delusions  were  elicited.  He  was  some- 
what euphoric.  Continually  attempted  to  leave  the  hospital ;  rather  verbose 
in  answers,  otherwise  showed  no  distinct  mental  symptoms ;  physical  signs 
were  carefully  noted  at  that  time.  The  left  pupil  was  slightly  larger  than 
the  right;  both  reacted  moderately  to  light,  consensual  and  distance.  Cranial 
nerves  of  the  face  were  good.  No  paralysis  anywhere.  Slight  tremor  of  the 
hands;  reflexes  of  the  arm  were  equal  and  moderate;  knee  jerks  equal  and 
active;  ankle  jerks  equal  and  active.  No  Babinski,  Gordon  or  Oppenheim. 
Adductors  moderate;  cremasters  and  abdominals  O.  K.  In  other  words. 
physical  examination  was  almost  entirely  negative.  Blood  serum  positive  to 
the  Wassermann  reaction  to  syphilis.  Spinal  fluid  showed  moderate  pres- 
sure, albumin  much  increased  Wassermann  negative,  globulin  by  Nonne'^ 
method  slightly  positive,  likewise  by  Noguchi's  method;  cells  mostly  red.  of 
which  there  were  perhaps  one  thousand  in  the  field.  No  blood  had  been 
drawn  upon  puncture,  and  these  cells,  it  is  evident,  had  not  come  from  the 
puncture,  since  the  slightly  yellowish  tinge  of  the  spinal  fluid  could  not  be 
centrifuged  out.  This  peculiar  spinal  fluid  had  its  explanation  a  very  shorl 
time  afterward  in  the  following: 

May  11,  during  the  morning,  the  patient  was  restless,  confused  and  at- 
tempted to  get  out.  At  12:30  he  suddenly  lost  consciousness,  became  rigid 
and  showed  some  clonic  movements.  Recovered  in  about  thirty  minute'^. 
During  this  time  there  was  a  double  Baliinski.  more  on  the  right  side,  rigid 
])upils,  absence  uf  abdominal  and  cremasteric  reflexes.  At  6:00  p.m.  he 
was  up  and  around,  very  euphoric  and  markedly  confabulating.  He  told 
how  he  had  been  out  all  day  in  an  automobile,  and  spoke  of  the  very  elabo- 


RANSOHOFF  MEMORIAL  VOLUME 


rate  meals  he  had  had.  Showed  marked  loss  of  memory  for  recent  events. 
Was  disoriented  for  time  and  place.  Gave  irrational  answers  to  questions 
on  educational  matters.  Lumbar  puncture  done  at  this  time  shows  that 
spinal  fluid  was  under  high  pressure,  was  yellowish  in  color,  and  contained 
very  many  red  cells,  although  no  blood  had  been  drawn  by  the  puncture, 
and.  as  before,  the  color  could  not  be  centrifuged  out.  The  Wassermann 
reaction  in  the  blood  was  still  positive.  At  this  time  there  was  positive 
U'assermann  reaction  of  spinal  fluid.  The  globulin  was  distinctly  positive. 
From  this  time,  for  a  period  of  a  month,  the  patient  had  marked  euphoric 
delusions.  He  was  to  marry  a  nurse  of  the  ward ;  he  had  $50,000,  a  motor 
boat,  and  a  Fierce-Arrow  automobile  was  to  take  him  and  his  bride  all  over 
this  country  and  to  Europe.  He  denied  that  he  was  married,  and  said  most 
emphatically  that  the  nurse,  who  was  possessed  of  all  the  virtues  of  her  sex, 
both  in  person  and  character,  had  promised  her  hand  to  him  as  soon  as  he 
could  get  out.  He  had  schemes  for  making  money.  Gradually  this  euphoric 
state  disappeared. 

TKi:.\T.MKXT 

Mav   14.  .45  gr.  neosalvarsan. 

May  21.  .45  gr.  neosaharsan. 

May  24,  20  c.c.  scrum  intradurallv  ;  Wassermann  reaction  serum  posi- 
tive. 

Ma\    2^.   .9  gr.  neosaharsan  ;  Wassermann  reaction  serum  negative. 

May  31.  30  c.c.  serum  intradurally:  \\'assermann  reaction  serum  nega- 
tive. 

June  6,  .6  gr.  neosalvarsan. 

June  7,  Wassermann  reaction,  serum  slightly  positi\e ;  20  c.c.  serum 
injected  intradurally.  Spinal  fluid  at  this  time  >liowed  still  the  slight  yel- 
lowish tinge,  although  no  red  cells  were  to  be  seen.  This  yellowish  tinge 
persisted  for  some  time,  and  was  probably  due  to  hemoglobin  and  to  dis- 
solved coloring  matter  from  the  red  cells.  Finally  it  disappeared  and  the 
fluid  became  clear. 

June  11.  .45  gr.  neosaharsan;  Wassermann  reaction  spinal  fluid  nega- 
li\e. 

June   14.  Wassermann  reaction  serum  positive. 

June   19.  .9  gr.  neosalvarsan. 

June  21.  30  c.c.  serum  intradurally;  Wassermann  reaction  serum  ncga- 
ti\  e ;  spinal  fluid  suggestion  of  positive. 

July  2,  .9  gr.  neosalvarsan. 

July  7,  30  c.c.  serum  intradurally.  Spinal  fluid  at  thi>  time,  live  cells: 
globulin  slightly  jjositive ;  albumin  distinctly  increased;  suggestive  positive 
Wassermann  serum  slightly  jjositive. 

July   16,  .9  gr.  neosalvarsan. 

Paijc  VJ6 


WILLIAM  RAVINE 


Tilly  19,  30  c.c.  serum  iiitradurally,  ten  cells;  globulin  strongly  positive; 
albumin  increased;  Wassermann  reaction  in  serum  and  spinal  fluid  negative. 

July  30,  .9  gr.  neosalvarsan. 

August  2,  Wassermann  reaction  serum  positive. 

August  9,  another  physical  and  mental  examination  was  made.  He  does 
not  remember  the  two  weeks  following  the  convulsions.  Following  that, 
however,  his  memory  is  clear.  He  laughs  at  his  former  delusions  concern- 
ing the  nurse,  likewise  his  wealth.  He  spontaneously  states  that  he  has  been 
losing  his  memory  for  some  time  before  he  came  to  this  hospital,  likewise 
losing  his  ambition,  and  that  he  was  cranky  at  home.  No  pains ;  occasional 
dizzy  spells.  Physical  examination  at  this  time  shows  very  important 
changes.  The  right  pupil  showed  almost  no  reaction  to  light ;  the  left 
showed  prompt  consensual  and  light  reaction.  The  right  arm  reflex  is  lively ; 
greater  than  the  left :  knee  jerks  are  equal ;  right  ankle  jerk  is  active ;  left 
ankle  jerk  very  slight.  No  L5abinski,  Gordon  or  Oppenheim.  Mental  ex- 
amination by  the  Binet-Simon  and  Healy  tests  showed  no  distinct  defects. 
By  careful  psychological  tests  for  memory  defect,  and  by  the  ordinary 
psychiatric  examination,  nothing  of  a  pathological  nature  was  found.  He 
took  an  active  part  in  the  social  life  of  the  ward,  and  was  one  of  the  lead- 
ing spirits  among  the  patients. 

August   13,  .9  gr.  neosalvarsan. 

.\ugust  16,  30  c.c.  serum  intradurally ;  Wassermann  reaction  serum 
slightly   positive ;   Wassermann   reaction   spinal   fluid  negative. 

September  13,  serum  positive ;  treatment  discontinued. 

October  29,  note  was  made  that  his  condition  was  unchanged. 

December  24,  discharged  to  the  Taunton  State  Hospital.  Diagnosis, 
general  jiaresis;  condition  unimproved. 

At  the  time  of  his  discharge  from  the  Psychopathic  Hospital,  the  pa- 
tient had  commenced  to  become  grandiose  again.  He  exhibited  eccentrici- 
ties of  conduct,  and  is  said  to  have  had  a  hysterical  outburst.  This  out- 
burst the  patient  describes  differently.  He  said  he  had  a  numb  feeling  in 
his  head  and  in  his  right  hand,  that  while  he  knew  the  words  he  was  to  say 
and  use  he  could  not  utter  them.  Neither  could  he  write,  although  he  could 
read  what  was  brought  to  him.  \\hen  he  attempted  to  make  himself  under- 
stood by  the  physicians  he  spoke  nonsense  and  realized  that  it  was  non- 
sense. By  his  description  there  was  a  cerebral  condition  of  some  kind, 
transitory  in  nature,  marked  by  motor  ai)hasia  and  confusion,  with  numb- 
ness of  the  right  hand. 

Physical  Examination  at  Taunton.  December  26. — At  this  time  the 
pupils  are  Argyll-Robertson  on  both  sides;  tremor  of  tongue;  blunting  of 
sensation  of  right  side  of  face ;  arm  reflexes  as  before ;  left  Achilles  di- 
minished. No  Babinski,  Gordon  or  Oppenheim.  Cremasterics  present. 
Left  upper  and  lower  abdoininal  absent ;  ophthalmoscopic  negative. 

JVIental  examination  at  this  lime  shows  verbosity,  pomposity,  euphoria 
and  delusions  of  grandeur,  mostly  of  a  sexual  character.     He  is  to  marry 


RANSOM  OFF  MEMORIAL  VOLUME 


a  nurse  at  the  Phychopathic  Hospital,  and  they  are  to  go  on  a  long  trip 
together.  He  is  to  furnish  the  home.  She  is  the  most  beautiful  and  vir- 
tuous of  women.  Orientation  is  intact ;  memory  is  good  ;  no  hallucinations  ; 
acts  ^uperior  to  his  environment ;  somewhat  irritable  and  troublesome  among 
the  ]iatients ;  ^^'assermanu  reaction  in  spinal  tluid  positive ;  albumin  mod- 
erately increased;  thirty  lymphocytes;  serum  positive. 

Snmiiiary. — This  patient,  at  first  considered  a  case  of  cerebral  spinal 
syphilis,  is  now  considered  a  general  paretic.  First,  the  history  of  cerebral 
accident ;  second,  the  euphoria,  grandiose  ideas,  etc. ;  third,  the  gradual  de- 
velopment of  Argyll-Robertson  pupils  and  the  gradual  change  in  reflexes ; 
fourth,  the  appearance  of  all  the  four  reactions  in  blood  and  spinal  fluid 
plus  the  albumin  increase  in  the  latter.  He  has  shown  fluctuations  in  the 
W'assermann  in  blood,  and  there  was  present  in  the  spinal  fluid  evidence 
of  a  hemorrhage  which  has  made  its  way  into  it.  Undoubtedly  the  first 
flare  up  was  a  hemorrhage  into  some  part  of  the  brain,  and  it  is  very  prob- 
able that  the  second  development  of  grandiose  ideas  started  with  some 
cerebral  attack.  It  is  to  be  especially  noted  that  the  Argjll-Robertson  pupils 
developed  in  this  case  despite  the  use  of  salvarsan  and  the  use  of  salvar- 
sanized  serum,  and  for  that  reason  I  think  this  case  of  crucial  importance 
in  determining  the  value  of  the  Swift-Ellis  method. 

It  is  claimed  that  the  value  of  the  Swift-Ellis  over  any  other  method  lies 
in  the  fact  of  the  inaccessibility  of  the  nervous  system  through  the  blood 
stream.  The  effects  of  bromide,  chloral,  opium,  alcohol,  strvchnia.  and 
certain  of  the  toxins  of  the  infectious  diseases,  seem  notably  to  affect  the 
brain  and  nervous  system  through  the  blood  stream. 

Professor  Benedict,  of  the  Cornell  Medical  School,  made  an  examina- 
tion of  four  specimens  of  spinal  fluid  twenty-four  hours  after  intravenous 
injection  of  salvarsan  (0.4)  and  found  that  the  spinal  fluid  contained  free 
arsenic  in  about  one-sixth  to  one-tenth  the  concentration  in  the  whole  blood. 
This  is  a  striking  fact  and  is  contrary  to  the  usual  belief  that  none  of  the 
drug  administered  intravenously  finds  its  way  into  the  spinal  fluid.  This 
same  investigator  found  more  free  arsenic  in  the  spinal  fluid  after  an  in- 
travenous injection  of  salvarsan  than  is  found  in  the  salvar>anized  serum 
as  used  for  intraspinal  injection. 

The  injection  of  a  serum  into  the  cerebro-spinal  siKice  can.  and  does, 
affect  a  condition  which  is  purely  meningeal  in  its  involvement.  In  tabes 
and  paresis,  in  addition,  we  have  a  destructive  process  present,  which 
condition  we  should  not  make  worse  by  the  intradural  injection;  also  the 
general  health  of  the  patient  must  be  conserved. 

"Forsake  not  an  old  friend,  for  the  new  is  not  cuniparal)le  lo  him.  A 
new  friend  is  as  new  wine ;  when  it  is  old  thou  shalt  drink  it  with  pleasure." 
Mercury  and  the  iodids  have  been  tried  in  countless  cases  and  they  have 
n(jt  been  found  wanting.  They  have  in  the  past,  and  will  in  the  future, 
benefit  our  cases  of  .syphilis. 


WILLIAM  RAllNE 


The  writer  has  been  able  to  bring  about  the  same  cytological  and  chem- 
ical changes  that  have  been  accredited  to  the  method  of  Swift-Ellis,  with 
mercury  and  the  iodids  alone,  and  in  some  cases  combined  with  salvarsan 
intravenously. 

A  case  that  I  treated  at  the  Kracpclin  Clinic  at  Munich  will  illustrate 
the  changes  that  can  be  brought  about  in  the  siiinal  tluid  by  the  use  of 
mercurial  rubs,  four  gni.  daily,  plus  one  intra\enous  injection  of  .9  neo- 
salvarsan. 

Mr.  J.  \\"..  aged  thirty-three,  was  brought  into  the  clinic  by  the  ijolice, 
December  11.  1913,  wlm  had  found  him  wandering  aindessly  about  in  the 
outskirts  of  Munich.  Physical  and  mental  examination  at  the  time  of 
entrance  revealed  the  following:  He  was  disoriented  as  to  time  and  place, 
there  was  a  marked  dysarthria;  no  delusions  of  grandeur.  Left  to  himself, 
he  wanders  aimlessly  about  the  examining  room,  bumping  into  chairs  and 
tables;  he  understands  spoken  language,  attempts  to  read,  but  confabulates; 
handwriting  is  unintelligible.  Physical  examination:  Pupils  are  unequal, 
react  sluggishly  to  light  and  accommodation,  ophthalmoscopic  examination, 
bilateral  choked  disc,  increased  patellar  arm  and  Achilles  reflexes ;  slight 
Romberg. 

Clinical  diagnosis,  paresis;  serological  diagnosis  was  lues  cerebri.  Was- 
.sermann  reaction  of  blood  ])ositive ;  Wassermann  reaction  in  spinal  fluid 
negative,  and  on  larger  concentrations  positive ;  globulin  reaction  was  posi- 
tive. Cells  in  spinal  fluid,  1,042,  the  largest  amount  they  had  ever  seen  in 
a  case  (the  serologist  who  counted  the  cells  with  me  considered  it  a  typical 
American  finding).  He  was  put  to  bed  and  given  mercurial  rubs,  four  gm. 
daily. 

December  16.  lumbar  puncture  was  done;  showed  949  cells;  other  re- 
actions same. 

December  22,  lumbar  puncture  was  done  ;  showed  749  cells ;  other  re- 
actions same. 

December  25.  luniljar  puncture  was  done;  showed  367  cells;  other  re- 
actions same. 

December  29,  lumbar  puncture  was  done;  showed  625  cells;  other  re- 
actions same. 

January  6,  lumbar  puncture  was  done;  showed  405  cells;  other  re- 
actions same. 

Choked  disc  at  this  date  is  almost  entirely  disajipeared ;  talks  rational 
and  is  oriented  as  to  time  and  place. 

January  13,  lumbar  puncture  was  done;  showed  200  cells;  all  the  other 
reactions  positive. 

January  14.  be  was  transferred  to  the  "Quiet  Division." 

January  20,  be  was  given   .9  neosalvarsan  intravenously. 

January  27.  lumbar  i>uncture  shciwed  lifty-live  cells,  with  all  the  other 
reactions  positive. 


RAXSOHOfF  MEMORIAL  VOLUME 


January  28.  his  relatives  took  him  out  of  the  hospital  against  the  advice 
of  the  hospital  stafif,  but  he  was  entirely  clear  mentally. 

Summary. —  (1)  Daily  rubs  of  mercury,  four  gm. ;  the  cell  count  was 
reduced  from  1.042  to  200,  and  after  one  intravenous  injection  of  neosal- 
varsan  it  was  brought  down  to  fifty-five  cells  per  c.cm.  (2)  Mentally  he 
had   entirely  cleared   u]i.      (3)    Choked   disc   almost   entirely   disappeared 

(4)  The  Wassermann  in  blood  and  spinal  fluid  remained  positive. 

Dr.  Sachs,  of  New  York,  bears  out  this  statement  in  a  series  of  cases 
that  they  have  had.  It  is  also  interesting  to  note  that  in  a  few  cases  that 
were  not  treated,  which  showed  a  decrease  in  the  cell  count  of  the  cerebro- 
spinal fluid  as  well  as  remissions  clinically. 

The  rationale  of  treatment  in  syphilis  of  the  central  nervous  system  is : 
(1)  Conserve  the  general  health  of  the  patient.  (2)  Increase  the  leuco- 
cytosis  of  the  patient,  as  we  know  in  this  way  all  infections  are  combated ; 
this  can  be  done  by  the  injection,  subcutaneously,  of  nuclei  acid.  Some 
European  investigators  believe  in  placing  the  patient  in  an  electric  light 
cabinet;  in  this,  produce  what  they  call  an  artificial  fever.  (3)  K.  I.  by 
mouth.  (4)  Mercury,  rubs  or  deep  muscular  injections.  (5j  Salvarsan  or 
neosalvarsan  intravenously  or  over  the  fascia  lata.  (6)  Periods  of  inter- 
mission of  the  anti-specific  treatment  for  one  of  tonics. 

Summary. — (1)  The  direct  introduction  of  salvarsan  and  neosalvarsan 
into  the  spinal  canal  has  been  almost  entirely  abandoned,  as  it  is  fraught 
with  the  greatest  amount  of  danger.  (2)  The  chief  reliance  in  the  Swift- 
Ellis  method  is  in  the  initial  intravenous  injection.  (3)  The  nervous  system 
is  accessible  through  the  blood  stream  as  arsenic  is  recovered  from  the  spinal 
fluid  after  intravenous  injection  of  salvarsan.  (4)  The  amount  of  arsenic 
injected  by  the  Swift-Ellis  method  is  only  infinitesimal,  and  the  changes 
brought  about  are  no  doubt  due  to  the  initial  intravenous  injection,  or  to 
the  repeated  lumbar  punctures,  or  to  the  dilution  of  the  cerebro-spinal  fluid. 

(5)  The  changes  brought  about  by  this  method  are  only  those  of  the  labora- 
tory ;  clinical  recoveries  are  not  reported ;  fatalities  have  resulted  and  cases 
have  been  decidedly  made  worse.  (6)  This  method  has  not  supplanted  the 
time-honored  use  of  mercury  and  K.  I.,  plus  our  new  addition,  s.ilvarsan. 
(7)  The  method  is  one  that  requires  the  greatest  care  as  to  asepsis,  requires 
a  full  laboratory  equipment,  and  can  only  be  used  in  a  well-organi,'ed  hos- 
pital, and  is  not  applicable  for  the  general  practitioner.  It  is  very  painful, 
opiates  having  to  be  given  to  relieve  severe  pains  in  the  extremities. 

BIBLIOGR.\PHY 

The  Tre:itment  of  Syphilitic  .\ffcctions  of  the  Central  Nervous  System  with  Especial  Refer- 
ence to  the  ITse  of  Intraspinous  Injection.  Swift-Ellis,  Archives  of  Internal  Medicine,  Vol.  12, 
No.  3,  page  331. 

Results  of  the  Swift-Ellis  Intradural  Method  of  Treatment  in  General  Paresis.  A.  Meyerson, 
Roston    Mel,    an<l    Sure,    Iniii..    May    7,    1914,    page    709. 

l'nf,i\ 'M.il.I-  (■^HMi'Ii  .Minn-  h'nllowing  an  Intradural  Injection  of  Neosalvarsan.  .\lfred  Gor- 
don.  Jnn,       \     M      \,    N,,x,„il.,  r   Jl,    1914.    page   1851. 

TIk  I.iii.,-i.,ii„I  l,,..iHi,,,t  ,.f  Syphilis  of  the  Central  Nervous  System  with  Salvarsanized 
Serum   nf    Slan.hiid   StrtLKlli.     Hanson   S.    Ogilvie.  Jour.   A.    M.    .\..    November   28.    1914,    page    1936. 

Modern  Method  of  Trcatm.nt  of  Syphilis  of  the  Nervous  Svstem:  Sachs- Straus-Kaliski.  Am. 
Jour.   Med.   Scs.,   November,    1914,   No.   512.   page   693. 

Page  500 


ON  THE  STRICTURES  OF  THE  MALE  URETHRA.* 

A.  RAVdOi.i.  M.D.,  F.A.C.S., 

Cincinnati. 

Anatotny. — The  male  urethra  consists  embryologically  of  two  parts,  a 
posterior  segment  beginning  at  the  bladder  and  ending  at  the  ejaculatory 
ducts,  and  an  anterior  segment  which  comprehends  the  remainder  of  the 
canal.  Considering  the  regions  of  the  body  in  which  it  lies  the  urethra 
can  be  divided  into  pelvic,  perineal  and  penile  portions.  In  relation  to 
strictures  it  is  beter  to  consider  the  urethra  as  of  prostatic,  membranous 
and  spongy  portions.  An  abnormal  narrowness  of  any  portion  of  the  canal 
of  the  urethra  constitutes  a  stricture.  Indeed,  a  simple  hardening  of  the 
mucosa  of  the  urethra  is  capable  of  forming  a  stricture.  The  urethra  is 
not  a  simple  canal  to  let  the  urine  pass,  but  it  acts  like  a  valve,  which  with 
its  muscular  layers  squeezes  out  the  urine  to  the  last  drop.  When  the  mu- 
cous membrane  has  been  hardened  and  changed  in  its  delicate  structure,  if 
yet  there  is  no  organic  narrowing  of  the  organ,  yet  the  hardened  mucosa 
prevents  the  last  drop  of  urine  from  coming  out,  one  or  two  drops  of  urine 
remain  beyond  the  hardened  mucosa  and  maintain  a  constant  irritation 
which  con.stitutes  the  so-called  gleet. 

The  urethra  has  not  the  same  calibre  all  the  way  through.  The  meatus, 
the  middle  of  the  pars  pendula  and  the  beginning  of  the  pars  membranosa 
are  naturally  somewhat  narrower.  Other  parts  of  the  urethra  are  enlarged, 
so  after  the  meatus  the  fossa  navicularis  is  much  larger,  before  the  pars 
membranosa  is  another  enlargement  forming  the  bulbar  urethra,  while  the 
prostatic  portion  is  an  enlargement  in  the  shape  of  a  triangle.  At  this 
point  the  ejaculatory  ducts  and  the  ]irostatic  ducts  open,  and  from  thi- 
point  infectious  materials  reach  those  organs.  The  pars  membranace.i 
runs  from  the  prostatic  portion  to  the  bulb  going  through  both  layers  of 
the  triangular  ligament,  surrounded  by  the  fibers  of  the  compressor  urethrfe 
muscle.  Behind  it  the  glands  of  Cowper  lie,  the  excretory  ducts  of  which 
open  at  this  point  in  a  narrow  space  the  least  distensible  of  all  parts  of 
the  urethra.  This  is  just  in  the  curve,  less  movable  because  it  is  firmly 
fixed  to  the  symphysis.  On  account  of  its  curve  the  anterior  wall  of  the 
mucosa  is  shorter  than  the  posterior. 

The  wall  of  the  urethra  is  formed  by  a  mucous  membrane  containin-^ 
a  rich  venous  plexus,  and  in  the  prostatic  and  membranous  tract  it  is  well 
clothed  with  muscular  tissue.  The  mucous  membrane  has  an  epithelium 
which  varies  in  the  ditiferent  parts  of  the  urethra.  The  proximal  two-thirds 
of  the  prostatic  portion  resembles  the  epithelium  of  the  bladder.  At  the 
pars  membranacea  the  epithelium  takes  the  aspect  of  the  columnar  type. 
This  epithelium  covers  the   rest   of   the   urethra   to   the   fossa   navicularis, 

•  I'loni    .\meiicaii   Joiunal    of    Smgery,    December.    19J0. 


RAXSOIIOFF  MEMORIAL  J'OLUMR 


where  it  is  changed  into  stratified  epithehiini.  T!ie  nieatns  is  the  continua- 
tion of  the  epidermis  covering  the  glans. 

The  muscular  fibers  are  some  striated  and  some  non-striated.  The  non- 
striated,  involuntary,  are  incorporated  in  the  wall  of  the  urethra,  while  the 
others  are  in  the  form  of  accessory  bundles  derived  from  structures  sur- 
rounding the  urethra.  Some  of  the  intrinsic  muscles  are  longitudinal, 
forming  the  first  coat,  and  some  are  transverse  or  circular.  The  circular 
fibers,  well  developed,  form  a  thick  layer  especially  towards  the  internal 
orifice.  The  removal  of  all  urine  at  the  end  of  micturition  is  due  to  the 
action  of  the  muscular  tunic. 

Varieties. — Stricture  may  be  spasmodic  the  result  of  the  contraction  of 
the  compressor  urethrte,  which  may  impede  temporarily  the  passage  of  the 
urine  from  the  bladder.  Keyes'  refers  to  this  condition — the  abnormal 
urination  in  nervous  individuals,  who  can  not  urinate  in  the  presence  of 
others.  After  an  operation  for  hemorrhoids  in  some  individuals  the  urina- 
tion becomes  difiicult  and  spasmodic.  This  kind  of  stricture  is  not  perma- 
nent, being  only  of  spasmodic  nature,  yet  it  must  be  relieved  to  avoid  dis- 
astrous consequences  in  the  urinary  organs.  In  these  strictures  the  use  of 
the  filiform  bougies  will  increase  the  irritation  while  a  good  size  catheter 
will  be  easily  passed  and  will  tire  the  spasms  of  the  muscle.  In  withdraw- 
ing the  instrument  no  grasping  is  found.  Sometimes,  however,  a  spas- 
modic stricture  co-exists  with  an  organic  one  and  the  spasmodic  stricture 
may  he  the  result  of  the  other. 

The  spasm  is  easily  overcome  by  the  use  of  hot  sitz  bath,  by  the  admin- 
istration of  opiates,  and  later  by  the  insertion  of  a  metallic  sound.  To 
prevent  recurrence  the  passage  has  to  be  dilated,  the  muscle  .stretched,  and 
in  order  to  diminish  the  sensitiveness,  the  instillation  of  a  few  drops  of  a 
solution  of  silver  nitrate  1  to  1,000  will  be  of  a  great  value. 

The  strictures  \\hich  we  shall  ctjnsider  here  arc  the  sequel  of  urethritis. 
They  consist  in  a  contracting  periurethral  formation  of  fibrous  tissue, 
after  the  reabsorption  of  the  infiltrating  elements  deposited  in  the  sub- 
mucous layer  during  the  inflammatory  process.  The  mucous  membrane- 
becomes  hard,  thickened  in  some  places;  the  lumen  of  the  urethra  is  not 
narrowed,  but  yet  the  function  of  urination  is  impaired.  This  can  be  con- 
sidered the  first  stage  of  the  stricture.  When,  however,  the  process  of 
infiltration  in  the  submucous  tissues  heals,  on  account  of  the  sclerotic  changes 
in  the  connective  tissues,  it  forms  a  scar,  which  retracting  the  tissues  causes 
the  narrowing  of  the  lumen  of  the  urethra.  Consequently  there  are  two 
kinds  of  strictures:  the  first  soft,  easily  yielding,  which  rarely  afTects  the 
dimension  of  the  urethra,  have  been  called  after  Otis  Zi'ide  caliber  stric- 
tures; the  second  kind,  formed  by  hard  retracting  tissue,  have  a  tendency 
to  narrow  the  caliber  and  are  known  as  organic  strictures. 

It  is  a  diflicult  task  to  state  when  the  large  caliber  stricture  begins  and 
when  it  ends,  but  it  is  true  that  the  large  caliber  stricture  is  the  beginning 
and  the  callous  stricture  the  end.     .\  stricture  can  be  formed  in  any  part 


A.  RAVOGLI 


of  the  urethra,  but  some  parts  are  more  subject  to  the  strictures  than  others. 
Thompson  reported  320  cases  of  strictures  of  tlie  urethra  of  whicli  54  were 
seated  in  the  beginning  of  the  urethra  from  the  orifice  to  two  and  one-half 
inches  of  the  pars  pendula ;  51  were  in  the  middle  of  the  pars  pendula ;  216 
were  found  in  the  subpubic  curvature  in  the  bulb  and  in  the  membranous 
urethra.  The  frequency  of  strictures  in  these  regions  is  due  to  the  fact 
that  they  are  exceptionally  vascular,  and  on  account  of  the  curve  the  chronic 
urethritis  is  apt  to  localize  at  those  points.  The  abundance  of  follicles 
in  the  bulbar  region  favors  submucous  exudation.  Traumatic  stricture  is 
found  more  often  in  the  membranous  urethra. 

A  stricture  may  be  formed  in  ten  or  twelve  months  after  the  apparent 
cure  of  urethritis,  while  others  are  noticed  a  period  of  years  afterwards. 

£//o/o(7_v.— Strictures  may  be  produced  by  trauma  or  by  gonorrhea. 
According  to  Thompson  and  Martin  those  from  gonorrhea  are  much  more 
frequent  than  the  others.  As  a  result  of  urethral  chancre  and  from  ulcer- 
ated gummata  we  have  seen  deformities  of  the  meatus  and  cicatricial  for- 
mations of  the  fossa  navicularis,  but  it  seems  that  stricture  of  the  urethra 
proper  are  chiefly  the  consequence  of  a  gonorrheal  process. 

A  stricture  may  be  alone,  but  not  rarely  do  we  find  more  than  one  strict- 
ure in  the  same  urethra.  Although  Thompson  in  his  statistics  amongst  270 
cases  of  strictures  has  found  only  44  cases  of  multiple  stricture,  yet  (".uyon 
has  established  as  a  rule,  that  strictures  of  gonorrheal  origin  are  multiple, 
while  those  of  traumatic  origin  are  single.  In  our  experience  with  strictures 
of  gonorrheal  origin  we  have  found  only  rarely  two  at  a  distance  from  each 
other  in  different  portions  of  the  urethra.  In  some  cases  a  gonorrhea! 
stricture  may  present  a  numlier  of  ridges  to  the  exploring  bougie  and  so 
give  the  sensation  of  multiple  strictures  while  pathologically  it  is  one. 

Gonorrheal  strictures  are  nuich  more  frequent  than  traumatic.  Thompson 
placed  them  at  75  per  cent.,  Martin  at  85  per  cent.  Gonorrhea  itself  i? 
sufficient  to  produce  stricture  and  this  is  the  cause  in  most  of  the  cases. 
In  some  cases,  however,  the  stricture  may  have  been  caused  by  gonorrhea 
and  trauma  together  as  in  the  injuries  of  the  urethra  resulting  from  the 
superstitious  suggestions  of  breaking  the  chordee,  or  from  caustic  injections, 
or  from  the  injudicious  use  of  instruments. 

Traumatic  strictures  have  been  found  to  be  the  result  of  a  fall  on  the 
perineum.  Prezzer^  referred  to  the  observations  of  Millee  of  seven  case.-, 
of  urethritis  caused  by  riding  on  the  biciycle,  and  two  cases  of  ruptures 
of  the  urethra  followed  by  stricture.  In  individuals  who  have  practiced 
masturbation  stricture  has  been  found,  being  the  result  of  tearing  of  the 
mucous  membrane  in  the  spasm  of  the  i^ernicious  act. 

Pathogenesis.  It  is  easy  to  understand  how  a  stricture  is  formed  in  a 
portion  of  the  urethra,  by  remembering  the  changes,  which  the  conjunctiva 
undergoes  in  a  case  of  gonorrheal  opthalmia.  The  gonococci  after  producing 
acute  urethritis,  have  an  inclination  to  enter  the  epithelial  cells,  and,  going 


RANSOHOFF  MEMORIAL  VOLUME 


through  them,  find  sheher  in  the  deep  epithehal  layer  towards  the  connective 
tissues.  Usually  they  limit  their  action  in  limited  portions  of  the  urethra, 
where  they  are  less  disturbed,  as  in  the  glands  lacunae  Morgagni,  in  the 
places  where  the  walls  of  the  urethra  are  closer  together  as  at  the  beginning 
of  the  bulbar  region.  A  chronic  inflammatory  process  results  with  an  infil- 
tration, which,  together  with  the  irritation  of  the  connective  tissues  of  the 
subepithelial  layer,  starts  the  papillary  proliferation.  At  this  point  by  means 
of  the  urethroscope  the  mucous  membrane  appears  dark  red,  granulated,  it 
is  somewhat  thicker,  hard  and  inelastic.  This  is  the  beginning  of  a  wide- 
caliber  stricture.  In  some  cases  in  the  spongious  tissues  a  kind  of  inflam- 
matory knot  is  formed,  very  painful,  hard  to  the  touch.  This  usually  does 
not  form  an  abscess,  but  is  reabsorbed.  When  the  infiltration  disappears 
the  afifected  trabeculae  of  the  spongious  tissue  shrink.  Their  connective 
tissues,  hardened,  undergo  a  sclerotic  process.  This  causes  atrophy  of  the 
spongious  body  with  narrowing  of  the  lumen  of  the  urethra,  and  formation 
of  the  stricture. 

It  is  not  always  an  acute  process  which  causes  infiltration  of  the  trabeculae 
of  the  spongious  tissue,  but  more  often  a  chronic  inflammatory  process  is 
equally  responsible  for  the  induration  and  the  infiltration  of  the  spongious 
tissue  of  the  urethra.  This  process  which  can  be  diffused  through  a  great 
tract  of  the  urethra  is  usually  limited  to  a  small  portion.  (See  illustration.) 
The  process  consists  in  the  increase  of  the  connective  tissues  of  the  trabe- 
culae, which  makes  the  alveoli  much  smaller,  and  the  delicate  spongious 
tissue  is  converted  into  a  hard  and  thick  degenerated  sclerotic  tissues. 

The  work  of  Vajda,  Neilsen,  Baraban,  Finger,  Wassermann.  Nadli  and 
Guyon  have  contributed  a  great  deal  to  clearing  up  the  pathology  of  strict- 
ures. It  seems  that  the  anatomico-pathological  process  is  the  same  through- 
out, which  from  the  chronic  urethritis  gradually  brings  about  the  stricture. 
In  the  urethritis  we  find  an  inflammatory  process,  which  is  localized  in  spots, 
aflfecting  the  epithelial  and  the  subepithelial  tissues.  In  the  beginning  the 
acute  stage  produces  infiltration  of  serum  and  of  small  white  cells,  which 
infiltrating  the  connective  tissues  causes  their  proliferation  and  so  their 
thickening  and  swelling.  Gradually  the  infiltrating  cells  are  reabsorbed, 
spindle  cells  go  on  forming  connective  tissue  bundles,  which  are  changed 
into  a  thick  succulent  superficial  cicatrix  covered  with  an  abnormal  epithe- 
lium. \\hen  these  alterations  have  diminished  the  elasticity  of  tlie  urethra  in 
its  deeper  layer,  and  when  the  cicatricial  formation  has  extended  to  the 
corpus  spongiosum,  then  the  portion  of  the  urethra  loses  its  elasticity,  its 
normal  caliber  is  narrowed  and  the  organic  stricture  has  formed. 

Of  course  that  portion  of  hardened  mucosa  retains  a  few  drops  of  urine 
which  remaining  behind  the  impediment  irritate  the  mucosa  and  maintain 
a  certain  degree  of  irritation.  Guiard^  thought  that  the  virulence  of  the 
urethritis  was  the  cause  of  the  production  of  the  stricture.  We  have  often 
found  strictures  following  cases  of  urethritis,  which  on  account  of  their 
mildness  had  been  neglected. 


A.  RAVOGLI 


The  strictures  have  been  described  as  linear,  annular,  irregular,  tor- 
tuous, etc.,  which  are  only  clinical  distinctions  to  indicate  the  quantity,  the 
fhape,  the  disposition  of  the  scar  tissue,  which  at  times  forms  a  thin  band 
and  at  other  times  an  irregular  mass. 

A  stricture,  post-mortem,  appears  yellowish-white  in  color,  hard  and 
fibrous  in  consistency,  of  different  sizes  and  shapes.  It  has  no  hyperemia, 
swelling  or  infiltration  when  seen  through  the  urethroscope  during  life.  The 
epithelium  is  thickened,  whitish  and  resembles  a  superficial  cicatrix.  The 
sub-epithelial  tissue  when  the  swelling  is  gone  does  not  show  much  change, 
microscopically,  but  in  some  cases  the  surface  is  ridged,  uneven  and  even 
nodular.  When  the  stricture  has  been  much  advanced  a  band  of  cicatrix 
replaces  the  mucous  membrane,  penetrating  into  the  corpus  spongiosum. 
Behind  the  stricture  the  canal  of  the  urethra  is  distended,  abraded  and 
superficially  eroded. 

Microscopic  examination  shows  the  epithelium  thickened,  its  cylindrical 
cells  in  condition  of  mucoid  degeneration.  Pus  cells  are  found  imbedded 
between  the  layers  of  the  epithelium  (Finger*).  The  thin  cylindrical  epithe- 
lial cells  are  converted  into  a  hard  thick  pavement-like  epithelium.  The 
change  of  the  cylindrical  into  plaster  epithelium  is  of  itself  a  cause  of 
necrosis  of  the  mucuos  membrane,  which  is  connected  with  the  alteration 
of  the   subepithelial  connective  tissues. 

In  recent  cases  the  infiltration  surrounds  the  lucunae  and  the  glands, 
which  imbedded  in  the  sub-epithelial  tissue,  after  a  while  become  atrophic 
and  disappear.  In  many  cases  the  inflammatory  process  remains  superficial 
and  produces  only  a  superficial  non-constricting  cicatrix.  In  other  cases 
the  process  is  deep,  affects  the  periurethral  tissues  as  far  as  the  corpus 
cavernosum  and  forms  a  thick  retracting  stricture,  as  a  result  of  cavernitis 
complicating  the  chronic  urethritis. 

There  is  a  great  difiference  in  the  amount  of  retraction  between  strictures 
of  large  caliber  and  those  narrowing  the  canal.  In  the  first  a  superficial 
thickening  of  the  mucosa  and  the  superficial  layer  is  formed,  which  de- 
prives the  portion  of  the  organ  of  its  elasticity  and  retains  a  few  drops 
of  urine,  maintaining  a  constant  irritation.  The  others,  thick,  hard,  deeply 
contracted,  will  scarcely  admit  a  slender  sound. 

Symptomatology.  The  symptoms  from  which  we  ascertain  the  presence 
of  the  stricture  in  the  urethra  are  some  suggestive,  some  subjective  and  some 
objective  or  physical. 

A  long-standing  gleet  will  suggest  the  presence  of  a  stricture.  The 
patient  in  the  morning  squeezes  out  of  the  meatus  a  little  drop  of  clear 
or  milky  or  even  creamy  fluid.  In  some  cases  the  fluid  is  scarcely  perceptible, 
becomes  dry  and  sticks  the  lips  of  the  meatus  together.  In  many  cases  of 
stricture  the  gleety  discharge  is  missing. 

Whether  a  gleety  discharge  accompanies  the  stricture  or  not,  the  urine 
shows  the  presence  of  shreds.   These  are  small,  short,  or  like  a  light  cloudi- 

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RAXSOHOFF  MEMORIAL  VOLUME 


ness.  while  at  other  times  they  are  heavy,  thick,  twisted  and  soon  sini<  to 
the  bottom.  On  account  of  the  increased  acidity  of  the  urine,  the  stricture 
is  irritated  and  contracts,  then  the  symptoms  of  posterior  uretliritis  grows 
worse,  and  the  urine  becomes  cloudy.  These  exacerbations  are  considered 
bv  the  patients  as  new  attacks  of  gonorrhea. 

At  this  point  the  patients  suffer  from  what  is  called  irritable  bladder, 
with  the  necessity  of  urinating  frequently  (Hirsch").  It  is  not  the  nervous 
bladder  but  a  catarrhal  inflammation  extending  from  the  posterior  urethra 
(0  the  neck  of  the  bladder,  which  causes  the  necessity  to  urinate,  when  it 
is  touched  or  slightly  distended  by  the  urine.  The  frequency  or  urination 
varies,  and  it  is  felt  especially  at  night,  compelling  the  patient  to  get  up 
several  times  to  empty  the  bladder. 

The  presence  of  urine  in  the  bladder,  on  account  of  the  irritability  of 
the  genital  organs,  causes  frequent  erections  at  night,  which,  although  not 
accompanied  with  loss  of  semen  are  troublesome  to  the  patient.  In  some 
cases  the  patients  have  frequent  loss  of  semen.  At  times  the  erections  are 
painful,  the  stricture  prevents  the  discharge  of  semen  in  the  sexual  act, 
which  either  dribbles  out  of  the  urethra  or  runs  back  into  the  bladder  and 
is  discharged  with  the  flow  of  urine.  In  many  cases  of  stricture  the  patients 
com]ilain  of  diminution  of  the  sexual  appetite  and  some  of  impotence. 

Siihjccli7-c  Symptoms — A  stricture  in  the  urethra  impeding  micturition 
causes  change  in  the  stream  either  during  the  whole  urination,  or  at  the 
beginning  or  at  the  end.  The  size  of  the  stream  may  be  reduced  sometimes 
to  a  mere  thread.  Often  the  stream  is  divided  into  two,  spurting  in  different 
directions,  at  times  it  is  tortuous  or  twisted.  The  projection  of  the  stream, 
which  is  the  result  of  the  intensity  of  the  contraction  of  the  detrusor  vesicae 
is  greatly  impaired,  and  the  last  drops  which  remain  behind  the  stricture 
dribble  out  without  any  force  of  expulsion.  In  some  cases  the  urine  begins 
to  flow,  then  stops  and  the  urination  is  finished  at  intervals.  Painful  mic- 
turition as  a  consequence  of  stricture  is  rare,  and  exists  only  when  cystitis 
or  prostatitis  has  developed,  or  when  the  urethra  on  account  of  inflammation 
is  sensitive  to  distension.  When  the  posterior  urethra  is  inflamed  pain  is 
felt  in  the  beginning  of  the  urination  and  at  the  end,  when  the  last  drops 
are  expelled. 

When  the  bladder,  still  normal,  cannot  emptv  on  account  of  tlie  strictured 
urethra,  this  may  cause  spasmodic  jiains.  The  pain  from  the  bladder  radi- 
ates towards  the  rectum  and  the  urethra.  ( )nly  in  rare  cases  the  stricture 
may  lead  to  retention  of  urine.  It  is  the  result  of  an  engorgement  of  the 
peristrictural  tissues,  which  arrest  the  normal  emission  of  the  urine.  Ac- 
cording to  \'alentine'''  this  condition  is  precipitated  by  alcuholic  or  by  sexual 
debauch. 

It  has  to  be  remembered  that  on  account  of  the  continuous  straining 
to  urinate,  the  patients  are  subject  to  hemorrhoids  and  also  to  rectal  pro- 
lapse. 


A.  RAVOGLI 


In  severe  cases  of  stricture  the  bladder  undergoes  a  process  of  inflamma- 
tion not  only  catarrhal,  but  parenchymatous  in  character.  The  ureters  and 
kidneys  are  also  badly  affected  by  the  continuous  pressure,  and  may  be  in- 
volved in  a  form  of  pyelonephritis.  The  presence  of  the  urine  back  of 
the  stricture  forms  a  dilatation,  which  may  let  the  urine  infiltrate  causing 
extravasation,  perineal  abscesses,  and  urinary  fistula. 

In  many  cases  the  stricture  of  the  urethra  is  responsible  for  sexual 
neurasthenia,  pruritis  of  the  perineum  and  rectum,  persistent  and  recurrent 
herpes  progentalis,  and  even  dyspepsia  and  pains  in  the  stomach. 

Objective  .symptoms  are  all  positive  signs  which  we  obtain  by  means 
of  instruments.  It  has  to  be  remembered  that  when  discharge  is  present, 
it  has  to  be  examined  microscopially.  If  there  are  gonococci  in  the  secretion 
it  is  dangerous  to  introduce  instruments.  In  this  case  it  is  better  to  have 
the  patient  treated  by  the  irrigation  method. 

When  no  more  gonococci  are  present  or  no  more  secretion  and  the  pa- 
tient shows  irregularity  in  urination,  in  order  to  ascertain  the  presence 
of  the  stricture  and  its  location,  we  introduce  a  blunt  steel  sound.  The  first 
time  we  use  a  sound  which  easily  enters  the  meatus  (10  or  12  American) 
which,  after  having  been  sterilized  and  well  luljricatcd  is  introduced  with 
great  gentleness. 

In  some  cases  the  sound  is  introduced  without  encountering  any  ob- 
struction until  the  bladder  is  reached,  but  when  the  instrument  is  withdrawn 
it  is  grasped  so  that  it  can  only  with  difficulty  be  taken  out.  This  symptom 
shows  the  presence  of  a  wide  caliber  stricture.  Before  concluding  that  there 
is  a  stricture,  the  possibility  of  urethral  spasm  has  to  be  eliminated.  In 
some  cases  the  irritation  from  the  presence  of  the  sound  provokes  a  reflex 
action  of  the  muscles  of  the  urethra  which,  contracting,  grasp  the  instrument. 
This  constriction,  however,  is  never  so  firm  and  permanent  as  an  organic 
stricture.  Furthermore,  when  the  constriction  is  the  result  of  the  stricture  a 
discharge  of  one  drop  of  mucous  milky  secretion  follows  the  withdrawal 
of  the  sound.  This  drop  of  secretion  is  of  urine,  mucous,  saline  particles 
of  the  urine,  which  had  remained  behind  the  strictured  point,  and  when 
the  sound  has  distended  the  stricture  it  finds  its  way  out  of  the  canal. 

In  some  cases,  in  order  to  ascertain  the  presence  of  a  wide-caliber  strict- 
ure, it  is  better  to  use  an  olive-shaped  bougie,  as  recommended  by  Pousson", 
Jurquet*,  and  \''alentine".  The  olive-shaped  bougie  is  easily  introduced,  but 
when  withdrawn  it  is  grasped  firmly  by  the  strictured  portion  of  the  urethra. 
In  other  cases,  when  the  stricture  has  already  impaired  the  lumen  of  the 
canal  an  obstruction  is  encountered  which  prevents  the  introduction  of  the 
sound.  Then  it  is  necessary  to  try  smaller  blunt  sounds  until  it  is  found 
possible  to  pass  the  stricture. 

When  the  presence  of  a  stricture  has  been  ascertained  it  can  be  easily 
located  in  the  different  portions  of  the  urethra,  and  can  also  be  measured  by 
means  of  olivary  bougies,  or  by  the  urethrometer  of  Otis.     In  reference  to 

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RANSOHOFF  MEMORIAL  VOLUME 


this  instrument  Lovenhardt"'  and  Stewart"  caution  the  surgeon  that  it  is 
dangerous  and  questionable  practical  utility. 

Prognosis. — In  a  general  way  we  may  state  that  strictures  of  the  urethra 
do  not  occur  as  after  as  is  commonly  believed.  Jurquet  in  1,420  patients 
with  diseases  of  the  genito-urinary  tract  found  133  cases  of  strictures  of 
the  urethra  of  which  25  were  of  large  caliber.  From  our  own  experience 
we  can  assert  that  the  incidence  of  strictures  has  greatly  diminished.  The 
active  propaganda  on  social  hygiene,  the  exact  knowledge  of  the  cause  of 
gonorrhea,  and  the  judicious  and  rational  treatment  at  the  reach  of  every 
practitioner  have  had  a  great  influence  in  this  diminution.  \on  Sehlen'- 
wrote  that  the  formation  of  a  stricture  is  scarcely  possible  when  a  well- 
directed  treatment  for  gonorrhea  is  applied.  To  this  has  to  be  added,  when 
I  he  patient  applies  early  to  the  physician,  and  when  the  physician  has  thor- 
ough knowledge  of  the  treatment. 

In  reference  to  the  stricture  itself  we  can  say  that  the  prognosis  depends 
upon  the  nature  and  the  location.  Traumatic  strictures  have  a  tendency  to 
contract  rapidly,  while  gonorrheal  strictures  have  slow  course.  Strictures 
of  the  perineal  urethra  are  more  difficult  to  treat  than  those  of  the  pars  pen- 
dula.  When  a  stricture  is  extensive  and  deep,  having  its  base  in  the  caver- 
nous tisues,  it  will  never  be  completely  cured.  It  will  be  relieved  by  the 
use  of  sounds  or  by  operation,  but  it  will  gradually  relapse. 

As  to  danger  to  life,  it  has  only  rarely  occurred  that  a  stricture  ha.^ 
caused  death.  In  rare  cases  death  has  been  the  result  of  extravasation  of 
urine,  followed  by  abscess  and  gangrene.  In  other  cases  death  has  been 
produced  by  chronic  uremia,  when  the  kidneys  have  been  involved  in  an  in- 
flammatory process.  In  other  cases  death  may  be  the  result  of  cachexia 
and  exhaustion  from  pain  and  from  the  torments  caused  by  an  old  im- 
passable stricture.  The  patients  lose  sleep,  fail  to  eat  from  the  unrelieved 
desire  to  urinate,  and  from  the  fatigue  and  the  labor  of  difiticult  urination. 

Treatment. — The  treatment  of  urethral  strictures  has  for  its  aim  to  en- 
large the  lumen  of  the  urethra  and  maintain  its  enlarged  caliber  by  dilata- 
tion. 

Dilatation  is  effected  gradually  and  gently  by  the  use,  of  sounds,  whicii 
massaging  the  scar  tissue  of  the  stricture  provoke  its  absorption.  Keyes 
stated  that  the  maximum  of  eiTect  is  produced  by  the  minimum  of  effort, 
which  coincides  with  the  opinion  of  Guyon,  that  the  effect  is  due  not  to  the 
pressure  of  the  sound,  but  to  its  mere  contact.  Passing  a  sound  by  force, 
will  tear  and  bruise  the  mucous  membrane  and  consequently  increase  the  in- 
flammatory reaction.  A  steel  sound  must  go  in  without  effort.  In  this  way 
the  presence  of  the  sound  will  be  able  to  lessen  the  congestion  at  the  point 
of  contact,  correct  the  irregularities  in  the  canal  and  stimulate  the  deeper 
tissues  to  a  reaction  so  as  to  soften  the  cicatrix.  In  our  practice  we  have 
entirely  abandoned  the  method  of  forced  dilatation  and  of  divulsion.  which 
some  years  ago  were  largely  applied  with  serious  consequences. 

Page   SOS 


A.  RAVOGLl 


When  the  stricture  is  yet  soft  or  in  a  semifibrous  stage,  it  can  be  easily 
removed  by  prompting  the  reabsorption  of  the  infilerated  elements  by  means 
of  gradual  dilatation. 

I'he  dilator  of  Oberlander  marked  a  great  progress  in  the  therapeutics 
of  strictures.  It  was  found,  however,  that  the  two  blade  dilator  was  not 
sufficient.  Kollman  has  given  us  his  admirable  dilator,  which  consists  of 
four  blades  which  open  in  opposite  directions.  The  instrument  when  closed 
is  not  larger  than  an  ordinary  sound  22  Charriere.  It  is  introduced  in  almost 
any  urethra  without  the  necessity  of  meatotomy.  We  have  used  the  dilator 
quite  often  for  many  years,  but  gradually  we  are  using  it  less  frequently, 
relying  mostly  on  the  use  of  steel  sounds. 

In  cases  of  hard,  cicatricial  strictures  it  is  not  easy  to  enter  with  dilators. 
Some  of  these  small  caliber  strictures  scarcely  admit  a  sound  less  than  15 
French,  others  admit  only  a  filiform  bougie.  The  treatment  begins  with 
small  soft  rubber  bougies;  steel  sounds  have  to  be  avoided  because  of  the 
danger  of  producing  false  passages.  In  the  treatment  of  these  strictures 
we  have  found  beneficial  the  application  of  electrolysis,  for  with  it  we  have 
accomplished  in  one  siting  that  which  we  could  have  obtained  only  in  week.^' 
treatment.  Mansell  MouUin''  claims  that  in  a  narrow  cicatricial  stricture 
a  current  of  10  to  15  milliamperes  has  made  the  scar  soft,  and  the  tissues 
capable  of  distension.  The  action  of  the  weak  currents  produces  a  serous 
exudation,  and  a  real  decomposition  of  the  fibrous  tissues  removing  the  hy- 
drogen with  the  kathode.  Strong  currents  have  to  be  avoided  as  they  cause 
cauterization  of  the  tissues.  For  ordinary  work  a  current  of  from  10  to  20 
M.  A.  is  sufficient.  The  electrolytic  sound  is  kept  at  the  place  of  stricture, 
pushing  it  gradually  and  gently  forwards.  After  a  short  time  it  is  noticed 
that  it  advances  and  the  stricture  is  passed.  When  the  sound  has  passed 
the  stricture,  it  is  left  from  three  to  five  minutes,  then  is  withdrawn.  The 
pain  accompanying  this  operation  is  so  insignificant  that  there  is  no  neces- 
sity of  local  anesthesia.  The  reaction  is  somewhat  more  than  that  which 
follows  the  introduction  of  an  ordinary  sound.  The  softening  of  the  stric- 
ture is  only  temporary,  and  the  use  of  steel  sounds  has  to  be  continued  to 
insure  a  permanent  cure. 

Levin'*  proposes  short  radium  applications  through  the  urethra  as  an 
adjuvant  to  instrumental  dilatation.  But  a  beneficial  effect  is  denied  by 
Ayres,'-''  who  in  two  hard  strictures  used  a  capsule  of  40  mm.  left  in  situ 
for  thirty  minutes.  In  one  case  retention  developed  and  in  the  other  acute 
urethritis.  In  both  cases  the  strictures  were  harder  than  before.  In  ob- 
stinate and  recurring  strictures  it  is  necessary  to  resort  to  urethrotomy.  In- 
ternal urethrotomy  in  the  perineal  portion  of  the  urethra  is  done  with  the 
dilatation  urethrotome  ui  Otis  or  of  Maisimneuve.  The  cutting  of  the 
stricture  is  not  free  of  any  danger,  as  sometimes  there  may  be  hemorrhage. 
The  benefit  is  temporary;  after  a  while  the  tissues  shrink  again  and  the 
stricture  needs  to  be  dilated. 

Page  Ml 


RAXSOHOFF  MEMORIAL  ]'OLVME 


In  some  cases  of  impassable  stricture  external  urethrotomy  by  perineal 
section  is  the  only  means  to  relieve  the  patient.  We  have  had  occasion  to 
perform  this  operation,  many  times,  with  beneficial  results. 

When  by  any  method  the  dilatation  of  the  stricture  has  been  obtained  the 
second  interesting  part  of  the  treatment  is  to  keep  the  stricture  dilated  and 
finish  the  treatment.  For  this  purpose  the  passing' of  sounds  with  Beneque- 
Guyon  curve,  leaving  each  in  for  three  to  five  minutes  answers  the  purpose. 
In  a  general  way  we  can  state  that  when  a  stricture  of  the  urethra  has  been 
dilated  to  a  caliber  of  25  to  30  French  it  can  be  considered  a  good  result. 

During  the  treatiuent  of  a  stricture  complications  may  arise  which  we 
shall  only  mention — epididymitis,  inflammation  of  the  stricture,  and  the  so- 
called  urethral  fever.  The  use  of  internal  urinary  antiseptics  such  as  salol, 
formaldehyde  ammoniate,  known  as  cystogen.  antiseptin  or  uretropin,  will 
clear  the  urine  and  will  prevent  septic  fever.  Before  and  after  the  dilata- 
tion an  irrigation  with  a  mild  solution  of  biborate  of  sodium  or  of  perman- 
ganate of  potassium  will  diminish  the  danger  of  epididymitis. 

The  last  remedy  to  save  trouble  is  the  hands  of  the  surgeon,  tiiorough 
sterilization,  and  from  beginning  to  end.  gentleness. 

REFEREXCES 

1.  Keycs,  IC.  h.  The  Surgical  Diseases  of  the  C.enilo  Uiiuaiy  OigaiLs.  New  York,  190J, 
p.   167. 

2.  Pezzer:  .\iin.  ties  .Maladies  iler  Oiganes  Genitoiiriiiaires.  189-1.  Kif.  Monats  f.  I'lact. 
Dcm..  Bd.   -xviii.   p.    58. 

3.  Guiard:     Les    Urethrites   Chroniques   chez    rhonime.      Paris,    1898. 

4.  Finger,   E. :    Klenorrhca  of  the    Sexual  Organs.      189-1. 

5.  Hirsch,  M.:  Die  Reizbare  Blase.  Centralbl.  Grenzgebiete  der  Med.  unci  Cliir..  U.  14.  15. 
1904. 

6.  Valentine,    F.   C:     Vesical    Retention   of   Urine.      Medical    News.   .Tinio    18.    1904. 

7.  Pousson:     Large    Retrecisseinents   de   I'urethre. 

8.  .Turquet:  Retrecissements  urethrales  de  large  Calibre.  .\nn.  des  Mai.  dcs  Oreancs  cenito- 
urinaircs.   1894,  No.  4. 

9.  \alentine:     1.   c. 

10.  Ldvenhardt:  Kongress  der  Deutschen  Ucrniat.  Gescllscbaft.  .Mav,  1894;  icf.  .Monatsheft. 
f.    Pract.    Dermal.,    Bd.    18,    p.    615. 

11.  Quoted  by  R.   VV.   Taylor:     The   Pathology   and   Treatment   of    \enereal    Diseases,    1895. 

12.  \'on  Sehlen :  Ziir  Friihbehandlung  der  Gonorrhea.  Monatscheft  f.  Pract.  Dermat., 
Ud.  xviii,  .Tune   15,   1894. 

13.  .Mansell  -Moullin:  Treatment  of  the  Strictures  of  the  Urethra  by  Electricity.  The  Lancet, 
1893.      No.   36,   ref.    Monatscheft   f.   Pract.    Derm..   Bd.   xviii. 

14.  Levin.  Isaac:  The  Scoi)e  of  Radium  Therapy  in  Diseases  of  the  Genito-Uiiiiary  Organs. 
The   Urologic  and   Cutaneous   Review,    Vol.    22,   No.    1,   .Tan.,    1918,    p.    6. 


.Ayres,  Winfield: 


A  CASE  OF  TIN  POISONING.* 

Mdsics  Salzi'R,  M.D.. 
Cincinnati. 

laiuiary  29.  l'J17.  II.  'SI.,  a  traxeling  salesnuin.  aged  59,  consulted  mc  on 
ae-count  of  a  feeling  of  coldness  or  chilliness  and  sore  throat.  He  said  that  he 
had  felt  chilly  for  a  week  or  more.  His  temperature  was  102.5  and  his 
throat  was  red.  His  tongue  was  very  much  coated.  He  had  a  full  upper 
and  lower  .set  of  false  teeth.  The  physical  examination  was  otherwise  nega- 
tive. I  sent  him  home  and  told  him  to  go  to  hed.  The  following  da)'  I  called 
on  him.  His  temperature  was  still  over  102,  and  both  tonsils  were  covered 
with  white  spots.  A  diagnosis  of  acute  tonsillitis  was  made  at  this  time.  In 
four  days  his  temperature  was  normal,  his  throat  had  cleared  up,  and  I  dis- 
charged him  as  cured. 

February  21,  or  three  weeks  later,  he  again  consulted  me,  saying  that  he 
was  not  a  bit  better  and  that  he  had  had  to  discontinue  his  business  trip  be- 
cause he  felt  bad.  He  still  felt  chilly.  This  chilly  feeling  would  be  relieved 
occasionally  by  hot  flashes.  On  arising  in  the  morning,  he  said  that  he  felt 
as  if  he  were  stepping  into  a  tub  of  ice-water.  His  throat  also  continued 
to  annoy  him.  He  had  indefinite,  vague  pains  in  his  extremities  and  the  back 
of  his  head.  The  examination  of  his  throat  was  negative.  He  said  that  this 
feeling  of  coldness  was  so  persistent  and  annoying  that  he  was  unable  to  eat, 
sleep  or  attend  to  his  business.  His  tongue  was  still  heavily  coated.  His 
blood  showed  3,500,000  red.  6,200  whites,  and  70  per  cent,  hemoglobin,  but 
there  were  no  morphologic  changes.  Repeated  examination  failed  to  reveal 
anything  outside  of  this  slight  anemia.  The  W'assermann  and  Hecht-W'ein- 
berg  tests  were  negative- 
March  3,  Dr.  Roger  S.  Morris  saw  him  in  consultation,  and  was  unable 
to  throw  any  further  light  on  the  case.  We  both  agreed  that  the  condition 
was  one  of  simple  anemia  following  the  attack  of  fever  and  sore  throat  in 
January,  and  advised  that  he  go  to  ( )ld  Point  Cf)nifort  for  a  rest.  He  did 
not  go,  but  continued  to  consult  me  daily  or  oftener.  His  chief  complaints 
were  the  feeling  of  coldness  and  the  soreness  in  his  throat.  Drs.  Iglauer  and 
Allen  both  examined  his  throat,  and  their  findings  were  negative.  His  tem- 
perature was  always  normal. 

March  22,  he  returned  with  the  same  complaints,  coldness,  irritation  or 
pain  in  his  throat,  and  indefinite  pains  in  his  legs,  arms  and  head.  I  ex- 
amined his  throat  again  but  found  nothing.  I  told  him,  however,  that  I 
would  touch  his  throat  up  with  some  silver  nitrate.  He  then  took  out  his 
lower  set  of  teeth,  and,  seeing  that  they  attracted  my  attention,  he  said  that 
the  teeth  were  set  in  tin.  This  statement  was  confirmed  by  his  dentist, 
who  stated  that  the  plate  was  made  of  Watt's  metal,  which  is  two-thirds 
tin  and  one-third  bismuth.      Innnedialely  the  possibility  that  the  case  was 

•Read   before   the    .\cj,U-iiiy    nl    Nre.lici.ic,    Cincinii.ai,    rel.iuaiy   2i.    IVIS.— I'lom    Jouniai    .\m.  i 


RAXSOHOPF  MEMORIAL  J-QLVME 


one  of  tin  poisoning  flashed  through  my  mind,  although  I  had  never  heard 
of  such  a  case.  I  reasoned,  however,  that  if  other  heavy  metals  could 
produce  poisoning,  possibly  tin  also  could  do  so.  The  patient  had  been 
wearing  this  lower  set  since  December  11,  1916,  or  about  one  month  before 
the  symptoms  began.  I  told  him  not  to  wear  the  lower  set  of  teeth,  which 
showed  evidence  of  corrosion  in  spots,  until  I  had  an  opportunity  of  look- 
ing up  the  literature  on  the  subject. 

The  literature  abounds  in  references  to  so-called  tin  poisoning  in  which 
tinned  foods  were  partaken  of.  The  symptoms  in  these  cases  were  con- 
fined to  the  gastro-intestinal  tract  and  were  those  of  an  acute  poisoning. 
I  was  able  to  find  references  to  only  two  cases  in  which  tin  had  been  ab- 
sorbed and  had  given  rise  to  constitutional  disturbances,  and  one  of  these 
was  reported  by  Jolles^  in  1901.  His  patient  showed  constitutional  disturb- 
ances due  to  wearing  silk  stockings  impregnated  with  tin  salts.  In  this 
case  the  predominating,  outstanding  symptom  was  this  feeling  of  coldness 
which  my  patient  complained  of.  Jolles  proved  that  his  was  a  true  case  of 
tin  ijoisoning  by  finding  tin  in  the  urine  of  his  patient. 

In  my  own  patient  the  urine  passed  on  the  day  following  the  discontinu- 
ance of  the  wearing  of  the  plate  contained  traces  of  tin.  No  other  speci- 
mens of  the  urine  showed  any  traces.  The  patient  was  placed  on  a  diet 
free  from  canned  foods,  and  a  few  days  later  the  stool  was  examined. 
.\ppro.\imately  5  gm.  of  dried  stool  contained  0.0021  gm.  of  metallic  tin. 
Several  subsequent  examinations  of  the  stocl  showed  the  presence  of  tin. 

.\pril  6,  1917.  or  fifteen  days  after  the  patient  had  discontinued  wearing 
the  plate,  13  c.c.  of  the  blood  contained  0.0015  gm.  of  tin.  No  other  foreig)i 
metals  were  found  in  the  blood.  The  patient  still  complained  of  the  same 
symptoms,  although  they  had  ameliorated  somewhat.  The  coating  from 
iiis  tongue  had  almost  disap[)eared.  Considering  the  marked  affinity  of 
tin  for  proteins,  it  is  not  remarkable  that  the  symptoms  continued.  I  pre- 
scribed potasisum  iodid  then,  and  on  the  13th  of  April,  or  one  week  later. 
20  c.c.  of  his  blood  contained  only  0.0005  gm.  of  tin,  showing  that  more  than 
two-thirds  of  the  tin  had  been  eliminated  during  the  week.  No  subsequent 
examination  of  the  blood,  urine  or  feces  showed  any  traces  of  tin.  The 
anemia  gradually  cleared  up. 

The  chemical  analyses  in  this  case  were  made  by  Mr.  F.  C.  Broeman. 
consulting  chemist,  and  also  by  Mr.  Clarence  Bahlman,  of  the  Cincinnati 
Department  of  Health.  They  made  their  tests  independently,  using  parts 
of  the  same  specimens,  with  identical  results. 

Considerable  experimental  work  has  been  done  with  regard  to  the  effects 
of  tin  salts  when  administered  to  animals.  Salant,  Kieger  and  Trenthardt' 
showed  that  after  subcutaneous  injections  of  soluble  tin  salts,  tin  was  found 
in  the  urine,  feces,  skin  and  liver.  The  gastro-intestinal  tract  was  shown 
to  be  the  chief  organ  for  the  elimination  of  tin. 


MOSES  SALZER 


Ungar  and  Bodlander^  and  Lehman*  showed  that  repeated  injections  of 
small  quantities  of  tin  into  animals,  over  prolonged  periods,  resulted  in  the 
death  of  the  animals.  The  efifects  were  manifested  in  the  alimentary  tract, 
the  general  nutrition,  and,  above  all,  in  the  central  nervous  system. 
Paralyses  of  the  extremities  were  frequently  observed. 

In  an  ex])eriment  conducted  by  Schryver,"'  a  dog,  weighing  8.5  kg.,  was 
given  20  mg.  of  tin  subcutaneously  in  the  course  of  several  days,  and  the 
animal  was  then  killed.  The  brain  and  cord  of  this  animal  weighed  65  gm. 
Twenty  gm.  were  submitted  to  examination  and  contained   1.5  mg.  of  tin. 

It  is  apparent  from  the  foregoing  that  tin  must  have  a  rather  strong 
affinity  for  nervous  tissue. 

I  lost  sight  of  the  patient,  and  did  not  see  him  again  until  September 
14.  1917.  He  came  to  me  complaining  of  the  same  symptoms,  but  in  a 
milder  form.  He  said  that  he  had  been  under  the  care  of  Dr.  Marion 
W'hitacre,  by  whom  he  had  been  sent  to  Dr.  Mithoefer.  who.  July  12,  1917. 
removed  his  tonsils  and  reported  both  badly  diseased.  I  saw  the  patient 
again,  October  17  and  November  1,  and  he  was  still  complaining  of  the 
same  symptoms.  He  was,  however,  attending  to  his  business  and  his  appe- 
tite was  normal. 

This  patient  has  since  passed  from  under  my  care,  and  the  last  I  heard 
of  him  he  was  making  the  "rounds"  from  one  [physician  to  the  other  still 
complaining  of  his  "hots  and  colds,"  although  he  is  now  able  to  attend  to 
business. 

The  onset  of  the  symptoms  within  a  few  weeks  of  the  patient's  starting 
to  wear  the  Watt's  metal  plate,  and  the  finding  of  the  tin  repeatedly  in  the 
blood,  stool  and  urine  by  two  chemists  working  independently  of  each 
other,  and  then  the  disappearance  of  tin  from  the  blood  after  the  patient 
discontinued  the  wearing  of  the  plate  are  to  my  mind  incontrovertible  evi- 
dence in  support  of  my  diagnosis.  His  symptoms  were  almost  identical 
with  those  of  Jolles'  patient. 

In  view  of  the  experiments  quoted  above,  in  which  so  much  tin  was 
found  in  the  nervous  system,  I  feel  reasonably  certain  that  this  man's  nerv- 
ous system  suffered  severely,  and  possibly  permanently,  which  accounts  for 
the  persistence  of  his  symptoms. 

"Ungar   and    Bndlander:     Ztsclir.    f.    Hyg.,    1887,    11,    J41. 
•Lehman:     Arch.    f.   Hyg.,    1902,   -45,    88. 
•  Schryver:    Jour.  Hyg.,   1909,  9,  2b.'. 


RHINOPHYMA.* 

M.  G.  Seeug,  M.D.,  F.A.C.S., 

St.  Louis 

Rhinophyma  is  an  essential  disease  of  the  nose,  of  more  than  ordinary 
interest.  The  gross  characteristics  of  the  disease  and  the  resuhant  dis- 
figurement are,  in  the  first  instance,  striking.  From  tlie  purely  cliiu'cal 
side,  the  uncertain  and  possible  multiplicity  of  etiological  factors  adds  in- 
terest. From  the  pathological  side  there  is  presented  the  interesting  prob- 
lem of  deciding  whether  to  classify  the  disease  as  an  inflammatory  hyper- 
trophy or  as  a  frank  neoplasm,  and  finally,  from  the  historical  point  of 
view,  the  disease  simulates  unusual  and  fascinating  interest,  nwing  to  the 
part  played  by  the  old  masters  of  classical  painting  and  satire  in  i)icturing 
the  disease  on  canvas  and  in  prints. 

From  the  clinical  side,  rhinophyma  might  be  descriljed  fairly  accurately 
if  one  merely  .';et  down  the  various  descriptive  terms  which  have  been  used 
in  naming  the  disease :  whiskey  nose,  pound  nose,  nodular  nose,  growing 
nose,  copper  nose,  elphantiasis  of  the  nose,  hypertrophy  of  the  nose,  lymph- 
angioma, acne  hypcrplastica,  iil)roma  molluscum  and  cyst-adeno-fibroma. 
In  the  earliest  stage  of  the  disease  the  nose  is  a  dark  copper  red.  and  there 
are  dark  red  spots  about  it,  particularly  on  the  cheeks  and  at  the  glabella. 
Gradually  there  appear  on  the  nose  lentil-size  to  pea-size  discrete  or  con- 
fluent nodules.  As  these  nodules  coalesce,  and  the  soft  parts  hypertrophy, 
the  whole  organ  becomes  deformed  by  the  tumor-like  nodules.  The  de- 
forming growths  occur  usually  at  the  tij)  and  on  both  ala".  and  may  De 
discrete  and  lolmlated.  or  the\  may  fusi',  fornnng  one  largt-  kmih.  Some 
limes  tJiey  are  i)eduncul;Ued.  \\m  ISruns  rep(iris  a  case  in  which  the 
growth  reached  to  the  chin,  and  bad  to  be  held  aside  when  tiie  [latiem 
partook  of  food  or  drink.  .\s  a  rule,  there  are  only  three  irregularl) 
rounded  lobulated  growths  situated  at  tij)  and  al;e,  but  sometimes  there 
are  many  small  lobes  separated  by  deep  furrows.  The  nodules  are  usually 
soft  and  are  coursed  by  dilated  veins,  and  studded  with  comedoes  and  acne 
pustules.  Owing  to  the  activity  of  the  sebaceous  glands,  the  surface  of  the 
nose  presents  an  oily  varnished  appearance,  and  seems  to  be  pitted  by  the 
wide  open  mouths  of  these  glands.  Pressure  on  the  nodules  causes  maca- 
roni-like plugs  of  sebum  to  worm  out  from  the  sebaceous  glands. 

The  disease  occurs  usually  in  the  fifth  and  sixth  decades,  that  is,  the 
deformity  is  complete  at  these  periods,  the  process  having  taken  live  tn 
twenty  years  to  develop  fully. 

There  probably  is  no  relationsliip  between  the  disease  and  alcoholism. 
An  analysis  of  the  cases  shows  that  there  is  an  infinitesimally  small  num- 

*Re.ld  at  the  mi-<rtilig  of  tllt  Western  .Surgical  .^ssociiiti..!!,  Kalis.is  I  ity.  i>i-(enil.i-r.  191y.- 
I'rum   Surgery.    |-.w„.,.,jl..i,.y    ,,,,,1    Oh^iet.  i.-s    .Npril.    19:0. 

/'one  an 


M.  G.  SEELIG 


ber,  compared  with  the  number  of  alcoholics:  and  that  many  cases  of  rhino- 
phyma  occur  in  non-drinkers. 

The  commonly  accepted  opinion  is  that  rhinopliyina.  pathologically  speak- 
ing, represents  the  terminal  stage  of  acne  rosacea  that  has  passed  llirough 
acne  hypertro])hica.  In  manj'  instances  the  disease  seems  to  rest  on  a  con- 
genital basis ;  Lassar  believed  that  there  was  a  predisposition  to  rhinophyma 
in  wide-pored  individuals.  The  essential  pathological  process  is  an  hyper- 
plasia of  tlie  connective  tissue  of  the  soft  parts  of  the  nose,  accompanied  by 
a  dilatation  of  the  blood  vessels,  and  hypertrophy  or  cystic  degeneration  of 
the  sebaceous  glands.  The  skin  follicles  show,  in  places,  di.stinct  evidences 
of  suppuration.  The  openings  of  follicles  and  of  the  ducts  of  the  sebaceous 
glands  are  widened,  so  that  they  resemble  deeply-pitted  pores,  often  giving 
to  the  nose  the  appearance  of   a   sponge.      Xo  one   has   e\er   satisfactorily 


Fig.  1.     Rhinophyma  lieforc  operatidii 
Fig.  2.     Profile,  saint-  patient. 


demonstrated  the  cause  of  the  disease.  Kai^osi  sought  to  prove  that  the 
connective-tissue  growth,  blood-vessel  dilatation,  and  sebaceous-gland  de- 
generation were  all  secondary  to  an  angioneurosis ;  but  there  is  no  marked 
consensus  of  opinion  concerning  this  theory.  Trendelenburg  considered  the 
disease  as  a  new-growth  and  grouped  it  under  the  head  of,  tibroma  mollus- 
cum  ;   L.assar  considered  it  a  cysto-adeno-fibroma. 

I  am  indebted  to  Dr.  Martin  Engman  for  the  privilege  of  quoting  from 
the  advance  sheets  of  his  forthcoming  book  on  Diseases  of  the  Skin.  Dr. 
Engman  from  an  intensive  study  of  rhinophyma,  draws  the  following  con- 
clusions regarding  the  pathology  of  the  disease :  "Rhinophyma  is  a  familial 
disease  representing  some  type  of  hereditary  transmission.  It  occurs  usually 
in  the  seborrhoeic  type  of  individual.  (The  seborrhceic  type  of  Sabouraud 
may  be  described  as  an  individual  with  yellows-tinted,  muddy,  thick  skin, 
the  yellowish  tint  being  most  pronounced  around  seborrhceic  areas,  with  a 
tendency  to  acne  vulgaris  in  youth  and  acne  rosacea  in  middle  life.)     'i'he 


RAXSOHOFF  MEMORIAL  VOLUME 


future  rhinophyma  subject  shows  a  tendency  toward  flushing  of  the  face, 
on  entering  a  warm  room,  after  meals,  or  under  excitement.  This  flushing 
leads,  in  time,  to  a  chronic  congestion,  with  secondary  chronic  infection  of 
the  skin  of  the  nose  and  sometimes  of  the  cheeks.  This  in  turn  leads  to  a 
chronic  ]:)roductive  inflammation,  w-ith  vascular  dilation,  connective-tissue- 
formation  and  dilation  of  the  sebaceous  glands  into  cyst  formations.  There 
is  a  marked  thickening  of  the  cutis  vera,  which  throws  the  skin  into  folds  and 
furrows.  The  end-result  is  the  multiple  formation  of  knobs  or  tumor-like 
masses." 

The  treatment  of  the  disease  is  exclusively  operative.  The  occasional 
recommendation  to  practice  wedge-shaped  incisions  should  be  ignored.  The 
most  satisfactory  operative  procedure  consists  in  shaving  ofT  the  redundant 
tissue  until  the  nose  is  brought  back  to  what  one  assumes  was  its  original 


Fig.  5.  Unknown  subject,  painted  bv  Holbein  the  vimnger  (1497-1553").  Hangs  in 
the  Prado  of   Madrid.     (From  HoUactidcr.) 

Fig.  6.  Portrait  of  supposed  grandfather  and  grandchild  of  Ghirlandajo  0449-1494). 
Hangs  in  the  Louvre.    (From  HoUacnder.) 

Fig.  7.  Unknown  sitter  bv  a  Holland  master,  in  Museum  at  Stockholm.  ( From 
Hollacndcr.) 

form.  In  this  shaving  process,  two  things  should  be  borne  carefully  in  mind : 
(1)  do  not  shave  too  deeply;  and  (2)  preserve  a  thin  rim  of  epithelium 
around  the  snares.  If  the  shaving  is  carried  too  deeply,  we  remove  all  se- 
baceous-gland rests  and  leave  no  niduses  of  epithelium  from  which,  as 
brood  centers,  epithelization  may  spread.  This  delays  healing,  and  even 
if  the  nose  be  grafted,  the  resultant  skin  has  a  harsh,  white,  dry  appearance 
so  striking  as  always  to  command  attention  and  cause  comment.  Further- 
more, deep  shaving  may  injure  the  nasal  cartilages  and  set  up  a  stubborn 
perichondritis.  If  a  thin  ring  of  intact  skin  is  not  left  around  the  snares, 
serious  disfigurement  may  result  from  the  contractions  incident  to  cicatriza- 
tion. H;emorrhage,  which  i.^  u.'~ually  very  free,  is  checked  with  comparative 
Page  r.ii; 


M.  G.  SEELIG 


ease  by  simple  gauze  pressure,  and  the  patient  is  sent  to  bed  with  a  large, 
well  vaselined  gauze  pad  over  his  nose.  The  next  day  this  pad  is  removed, 
and  the  denuded  area  is  strapped  with  imbricated  strips  of  sterile  zinc  oxide 
adhesive  plaster.  This  plaster  dressing  is  changed  daily.  Under  this  simple 
dressing,  my  patient,  shown  in  Figures  1  to  4,  was  completely  healed  in  ten 
days.  It  is  not  necesary  to  skin  graft  these  patients.  Indeed,  von  Bruns 
[Joints  out  that  grafting  often  leads  to  the  development  of  retention  cysts 
underneath  the  grafts,  with  subsequent  breaking  through  and  ulceration. 

The  role  that  rhinophyma  plays  in  medical  history  and  in  classical  art 
and  caricature  is  not  totally  without  interest  even  to  a  group  of  practical 
surgeons.  Dr.  Eugen  Hollaender  in  his  two  volumes  devoted  to  Medicine  m 
Classical  Art  and  Caricature  and  Satire  in  Medicine  furnishes  some  strikin:^ 
copies  of  pictures  that  feature  rhinophyma. 


Fig.  9. 
Fig.  II 


C.erhard  Janssen,  an  old  gias.';  etcher  of  the  middle  seventeen 
tury.      (From   Hollaender.) 
.\  caricature  from  the  seventeenth  century.     One  of  the  so-called   Kings  of 
Noses.     (From  Hollaender.) 
.\  caricature  of  a  physician,  published  about  1700  in  Augsburg.      (See  text 
for  translation  of  legend.)      (From  Hollaender.) 


Hans  Holbein,  1497-1553  (known  as  Holbein  the  younger),  famous  in 
medical  art  as  the  painter  of  the  Dance  of  Death,  painted  the  portrait  of 
an  unknown  subject  (Fig.  5).  The  portrait,  which  hangs  in  the  Prado  at 
Madrid,  shows  an  old  man,  with  a  typical  rhinophyma,  and  the  characteristic 
red,  congested  color  scheme  which  goes  with  this  disease.  Hollaender  states 
that  the  coloring  seems  to  have  been  toned  down  by  the  artist,  in  order  to 
minimize  the  existence  of  the  disease  as  much  as  possible. 

Donienico  Ghirlandajo,  1449-1494,  the  famous  Florentine  artist,  has  a 
I)iclure  in  the  Louvre  illustrating  rhinophyma  even  more  typically  (Fig.  6). 


A'. IXSOIIOJ^ MJ^MORIAL  I'OLUMI: 

HoIIaeiider's  speculations  of  this  particular  picture  are  interesting  rather 
than  convincing.  He  queries  as  to  whether  the  small  tumor  on  the  right 
brow  of  the  old  gentleman  may  not  be  intended  as  a  metastasis,  thus  hint- 
ing at  the  possible  belief  that  rhinophyma  was  at  that  time  considered  to  be 
malignant.  Then  further,  he  speculates  as  to  whether  the  beautiful  child's 
head  was  intended  to  soften,  by  contrast,  the  jarring  asymmetry  of  the  bul- 
bous nose  of  the  old  gentleman,  or  whether  the  perfect  featured  little  grand- 
daughter was  used  to  disprove  the  familial  nature  of  the  disease. 

Hollaender  presents  these  two  pictures  (Figs.  5  and  6)  and  the  picture 
by  an  unknown  Holland  master  (in  the  museum  at  Stockholm,  Fig.  7)  to 
illustrate  the  fact  that  they  are  pure  portraiture,  artistically  executed  with- 
out a  semblance  of  caricature.  These  portraits  may  stimulate  a  sense  of 
sympathy  but  they  make  no  appeal  whatsoever  to  the  risible  in  our  make-up. 

By  contrast.  iMgure  S  leads  away  from  art,  into  the  field  of  caricature. 
This  old  rhinophyma  subject.  Gerhard  Janssen  by  name,  was  a  master  glass 
etcher,  born  in  Holland  and  trained  in  his  art  at  Dresden,  1650-54.  The 
print  itself  is  not  a  caricature,  but  the  descriptive  phrases  engraved  about 
it^  furnish  a  caricaturish  setting:  such  phrases,  for  example,  as  the  legend 
just  aljovc  the  head.  Xasiitits  scd  aciitiis  (large  nosed  but  wise)  and  the  sen- 
tence in  the  frame,  Es  ist  ■:caiir  cin  iinfocrnilichc  Nasc.  abcr  sinnrcichcd  J'cr- 
staiul  (a  misshapen  nose,  'tis  true,  but  talented  and  wise). 

The  next  two  prints  arc  frank  caricatures.  Figure  9  is  from  an  old 
seventeenth  century  pamphlet  and  is  a  simon-pure  bit  of  what  Hollaender 
calls  naive  lack  of  humor  of  this  period.  This  king  of  The  Large  Nosed 
stands  surrounded  by  all  sorts  of  impossible  things,  people,  animals,  a  large 
horn,  a  mercury  staff,  a  shepherd's  staff,  ships,  etc.,  and  points  proudly  to 
his  rhinophymistic  organ. 

Figure  10  is  an  even  grosser  caricature,  and  represents  the  tendency  at 
this  particular  time  (late  1600)  to  use  the  doctor  as  a  scapegoat  and  har- 
lequin in  jokes  and  on  the  stage.  This  large-nosed  doctor,  with  what  might 
be  construed  as  a  rhinophyma  knob  at  the  proximal  and  middle  third  of 
his  proboscis  jiroclaims  : 

"For  healthy  people,  I  am  a  doctor,  God  help  tlie  sick. 
My  large  licadgear  embraces  profound   and  numerous   thoughts. 
My  costume  connotes  the  art  that   I  possess. 
W  hat  may  be  concealed  in  the  urine,  my  long  nose  detects." 


1  Tlic   kn.iul  abuu 

I   the   frame   is  a: 

S     folloHM 

.\    niisshapiii    nose 

■   indeed,   bnt   a   . 

man   of   t: 

prMsc  and  reward. 

The   Ic-gend   luukr 

ne.uh  tin-  i.ictuic 

:^: 

Ilerv    Gerh.iwl    I, 

from    16S0"to    !■- I        1 

eighty-eight   yea.-,    u 

.Uily   25,1725.    l.y    1 

! '     M_.  '•■;'■■   ■    ■■. 

M.  G.  SEELIG 


And  finally,  Figure  11  is  not  without  interest  from  an  ethnological  poinl 
of  view.  Rhinophyma  is  fairly  common  in  the  American  Indian.  This  is  a 
portrait  of  \\"a-Ha-Gun-Ta,  chief  of  the  Chippewas  (photographed  hy  Mr. 
William  Burton,  of  St.  Louis,  wlio  kindly  loaned  me  this  copy).  There  arc 
authentic  records  to  show  that  the  chief  is  about  127  years  old.  and  as  far 
as  the  memory  of  man  runs  he  has  had  a  typical  rhinophyma. 


i^^€  ^ 

^^^WrH-'- 

^^^^^k  ^^i<i'''/^:^^^*rfl 

Fig.  11.  Chief  VVa-Ha-Gun-Ta  ( .\mcrican  name  is  Capt.  John  Smith)  of  the 
Chippewas.  Still  living,  and  an  active  hunter  in  Glacier  Park,  at  an  approximate 
age  of   127  years.     Rhinophyma  is    fairly   common   in   American   Indians. 


ANATOMY  AXD  PATHOLOGY  OF  THE  SEMINAL  VESICLES.* 

E.  O.  Smith.  M.D., 

Cincinnati. 

The  seminal  vesicles  were  first  described  by  Fallopius,  1562,  and  may, 
therefore,  be  designated  as  the  male  Fallopian  tubes.  Further  analogy  be- 
tween the  Fallopian  tubes  of  the  female  and  the  seminal  vesicles  of  the 
male  rests  on  the  fact  that  both  are  not  only  frequently  involved  in  in- 
flammatory conditions,  but  both  are  often  the  seat  of  gonorrheal  infection. 

Allow  me  to  state  here  that  the  basis  of  this  discussion  was  a  prolonged 
study  of  many  post-mortem  specimens  of  the  seminal  vesicles,  prostates 
and  urinary  bladders  obtained  from  the  Pathological  Institute  of  the  Cin- 
cinnati General  Hospital. 

The  seminal  vesicles  are  located  between  the  urinary  bladder  and  th; 
rectum,  above  or  posterior  to  the  prostate  gland,  and  external  to  the  vasa 
deferentia.  The  duct  from  the  vas  joins  a  similar  tube  from  the  vesicle 
forming  the  ejaculatory  duct,  which  with  a  corresponding  structure  from 
the  opposite  side  passes  between  the  posterior  and  lateral  prostatic  lobe> 
terminating  near  the  anterior  jjortion  of  the  veruniontanuni  or  within  the 
sinus  pocularis. 

The  lower  jiortion  of  the  vesicle  rests  upon  the  ])osterior  border  of,  and 
is  with  difliculty  separated  from,  the  prostate.  This  is  particularly  true  if 
there  has  been  chronic  inflammation  of  these  parts.  The  general  direction 
of  the  long  axis  of  the  vesicle  is  upward  and  outward  from  the  posterior 
border  of  the  prostate  for  a  distance  varying  from  6  centimeters  to  22  cen- 
timeters. The  angle  of  divergence  varies  in  different  individuals,  and  may 
vary  greatly  in  the  same  individual,  this  depending  upon  a  collapsed  or 
dilated  condition  of  the  urinary  bladder.  The  greater  the  bladder  disten- 
sion, the  farther  are  the  upper  j)o!es  from  the  mid-line. 

This  is  an  important  fact  to  bear  in  mind  when  massaging  or  stripping 
the  vesicles.  In  many  cases  where  there  has  been  a  prolonged  obstruction 
to  the  outflow  of  urine  from  the  bladder,  the  long  axis  of  the  vesicles  is  at 
almost  right  angles  to  the  vertical  or  mid-line  of  the  body. 

Except  in  very  short  vesicles  the  upper  pole  extends  to  and  in  most 
specimens  overlaps  the  ureter  where  it  enters  the  outer  surface  of  the 
bladder.  The  vesicles,  except  the  lowest  portion,  are  external  to  that  part 
of  the  outer  wall  of  the  bladder  which  corresponds  to  the  trigone,  and  are 
held  in  contact  with  this  portion  of  the  bladder.  This  accounts  for  the 
vesicle  and  urinary  symptoms  that  so  often  accompany  vesiculitis  and  peri- 
vesiculitis.  It  might  be  added  that  the  aforementioned  symptoms  have 
frequently  been  treated  empirically  without  regard  to  cause. 

ological    .Association.    North    Central    Section.    Cliicago.    Novcru- 


E.  O.  SMITH 


The  close  relation  of  the  upper  portion  of  the  vesicle  to  the  ureter  ex- 
plains many  cases  of  narrozved  ureters  due  to  impingement  on  the  ureter 
of  a  pathological  vesicle  and  its  consequent  thickening,  plus  the  perivesicu- 
lar  inflammatory  tissue.  All  who  do  cystoscopic  work  have  had  the  experi- 
ence of  being  unable  to  introduce  the  ureteral  catheter  more  than  three- 
fourths  of  an  inch  to  one  inch,  yet  there  was  urine  flowing  from  the 
ureter.  There  can  be  no  doubt  but  that  this  failure  is  often  due  to  a  nar- 
rowing of  the  lumen  of  the  ureter  and  a  fixation  of  it  by  these  external 
adhesions  from  the  vesicle.  As  a  result  of  the  fixation  there  is  an  angula- 
tion which  the  ureteral  catheter  can  not  readily  pass.  It  is  a  well-estab- 
lished fact  that  a  normal  kidney  may  take  bacteria  from  the  blood  stream 


Fig  1.     Showing  relations  of  vesicles  tci  prostate,  vasa  deferentije.  bladder  a 

and  deposit  them  in  the  urine  stream  without  damage  to  the  kidney  itself. 
It  has  further  been  demonstrated  that  even  partial  obstruction  of  the  ureter 
will  sufficiently  lessen  the  normal  activity  and  resistance  of  the  kidney  so 
that  it  becomes  easy  prey  to  bacteria  in  the  blood  stream. 

Following  these  facts  a  little  further  it  requires  no  great  strain  on  the 
imagination  to  see  how  chronic  vesiculitis  and  perivesiculitis  can  be  a 
predisposing  factor  in  the  development  of  infections  of  the  kidney. 

Continuing  from  the  posterior  border  of  the  prostate  is  a  facial  inciii- 
brane  which  extends  beyond  the  vesicles.  This  can  easily  be  separated 
from  the  normal  vesicle,  but  with  much  difficulty  where  there  has  been 
perivesiculitis. 

Barnett  called  attention  to  the  importance  of  getting  beneath  this  fascia 
when  attempting  to  expose  the  vesicles,  either  for  drainage  or  removal. 
This  line  of  cleavage  once  found,  the  rectum  is  safe  from  puncture.  Be- 
neath this  fascia  is  found  a  much  thinner  fascial  layer  which  envelops  the 
vesicle  and  ampulla  of  the  vas  deferens.     Beneath  this  are  other  bands  of 

Page  HJI 


RAXSOinJff  Ml-.MUkl.lL  fOLUME 


fascia  that  hold  in  place  the  various  loops  and  saccules  of  the  vesicle.  The 
normal  vesicle  is  easily  detached  from  all  its  surroundings  except  at  the 
upper  pole,  where  the  blood  vessels  enter  and  at  the  lowest  i)art  which  i> 
in  contact  with  the  prostate.  In  doing  a  vesiculectomy  the  vessels  at  the 
upper  pole  should  be  ligated  before  removal  of  the  vesicle  to  prevent 
troublesome  or  possible  fatal  hemorrhage.  The  loss  of  blood  from  a  vesicu- 
lotomy or  simple  drainage  operation  is  negligible. 

In  about  one  of  every  ten  specimens  examined,  the  prritonriiui  ex- 
tended well  down  on  the  vesicles  and  occasionally  to  tiie  posterior  border 
of  the  prostate.  In  such  cases,  one  would  be  dangerously  near  the  peri- 
toneal cavity  when  operating  on  the  vesicles. 


?gostUc 


Long   axis   of   vesicles    I'orms   nearly   right   angles   with    long   axis   of   body. 
Upper,  outer  half  of  right  vesicle  contains  pus. 


One  specimen  disclosed  no  distinct  vesicles,  but  mere  rudiments  about 
one-half  inch  in  length. 

Picker  in  a  paper  before  the  Fourteenth  International  Medical  Congress 
held  in  London,  1913,  grouped  the  vesicles  according  to  their  anatomical 
arrangement  in  five  classes:  (1)  The  simple  straight  tubes;  (2)  thick 
twisted  tubes  with  or  without  diverticula;  (3)  thin  straight  or  twisted  tubes 
with  or  without  diverticula;  (4)  straight  or  twisted  main  tube  with  large 
grape-like  diverticula;  (5)  short  main  tube  with  large  irregular  ramified 
branches.  This  seems  to  be  an  unnecessary  multiplication  of  classes  as  the 
large  majority  of  the  specimens  I  examined  were  of  the  continuous  tubular 
type,  not  twisted  but  folded  at  sharp  angles  upon  themselves  many  times. 
Most  of  the  other  varieties  were  simple  modifications  of  this  type.     There 


J:.  O.  SMITH 


were  a  few  pear-shaped  vesicles,  whose  interior  had  the  appearance  of 
multiple  saccules  communicating  with  a  common  chanel.  or  vestibule,  but 
not  a  distinct  tube  or  tubule. 

The  most  iuiportant  anatomical  feature  of  the  vesicle  from  a  clinical 
or  pathological  viewpoint  is  the  multiple  sharp  angulations  of  the  tubule 
in  a  vast  majority  of  the  specimens.  There  can  be  no  emptying  of  the 
vesicles  except  by  some  sort  of  a  peristaltic  wave  which  must  begin  at  the 
blind  extremity  and  travel  along  the  tube  towards  its  outlet  into  the  ejacu- 
latory  duct.  I  am  inclined  to  believe  that  much  of  the  benefit  that  patients 
derive  from  a  properly  executed  massage  of  the  vesicles  is  due  to  a  stimu- 
lation of  this  normal  peristaltic  wave.     \ery  much   on   the  same  principle 


v*^ 


r*eritoneum  extends  to  prostate 


veniiK  \  e^ 
ight   side 


iasa.    Has  been  removed 


as  the  old-time  massage  and  kneading  of  the  abdomen  to  encourage  intes- 
tinal peristalsis,  before  the  days  of  Lane's  kink,  Jackson's  membrane  and 
Russian  oil.  "A  properly  executed  massage,"  therefore,  is  a  treatment  that 
is  not  to  severe  and  does  not  produce  trauma. 

The  appearance  of  the  interior  of  a  normal  vesicle  is  that  of  fine  tra- 
bcculations,  suggesting  irregularly  arranged  spider  webs  or  tendrils.  When 
this  condition  does  not  present  and  the  tubules  or  saccules  arc  smooth  in- 
side, there  has  been  suppuration  with  destruction  of  the  mucous  lining. 

The  vesicle  wall  is  constructed  of  three  layers  of  tissue,  'i'lic  outer  is 
a  fibrous  layer,  beneath  this  is  a  middle  layer  of  muscular  tissue,  which 
produces  the  peristaltic  movements  that  eiupty  the  vesicle.  The  interior  is 
covered  with  a  mucous  membrane  which  probably  has  some  secretory  func- 
tion, not  fully  and  satisfactorily  explained.  The  arrangement  of  the  tu- 
bules gives  a  very  extensive  mucous  surface  with  the  zvorst  natural  drain- 


RAXSOHOFF  MFMORIAL  J-QLUME 


age.  This,  partially  at  least,  accounts  for  the  fact  that  about  50  per  cent, 
of  the  post-mortem  specimens  examined  were  in  some  way  pathological. 
The  farther  up  the  tubule,  near  the  blind  end,  the  more  difficult  is  the 
drainage,  hence  we  would  expect  to  find  most  of  the  pathological  condi- 
tions in  the  upper  portions  of  the  vesicles,  where  they  are. 

Our   findings   in   these   specimens   demonstrate   that  a   simjile  single   in- 
cision,  especially   in   the   lower  [lart   of   a   vesicle   containing  pus,   will   not, 


^^J/^/ 


Fig,  4.     \-csicl 


can  not,  establish  satisfactory  surgical  drainage.  To  drain  properly,  mul- 
tiple incisions  are  required,  particularly  high  up  on  the  vesicle.  Judging 
from  the  specimens  alone  one  would  be  led  to  the  conclusion  that  nothing 
.short  of  a  vesiculectomy  could  be  effective,  yet  we  know  from  practical 
experience  that  thorough  vesiculotomy  is  followed  by  the  most  satisfactory 
results  in  properly  selected  cases. 

While  these  structures  were  discovered  by  Fallopius  in  the  sixteenth 
century,  and  recognized  as  the  seat  of  inflammation  by  Morgagnii  in  the 
eighteenth  century  (1745),  it  remained  for  Fuller  and  Belfield,  about  the 
beginning  of  the  twentieth  century,  to  bring  to  our  attention  the  importance 

Page  Sli 


E.  0.  SMITH 


of  these  hollow  organs  as  the  hiding  place  for  numerous  bacteria — prin- 
cipally Neisser's  diplococcus,  and  its  associates,  the  staphylococcus,  the 
streptococcus  and  the  colon  bacillus.  It  was  they  who  demonstrated  the 
relation  between  chronic  seminal  vesiculitis,  chronic  recurrent  urethral  dis- 
charge, and  certain  cases  of  arthritis.  Invasion  of  the  vesicles  by  bacteria 
from  the  posterior  urethra  is  certainly  a  simple  matter,  there  being  required 
only  a  short  trip  through  the  ejaculatory  duct,  a  distance  of  little  more 
than  one  inch.  Theoretically,  at  least,  one  would  suppose  from  the  very 
nearness  of  the  vesicles  to  the  posterior  urethra,  as  compared  to  the  epi- 
didymis, that  the  vesicles  would  be  more  frequently  involved  in  secondary 
infection  than  in  the  epididymis.  Who  can  say  they  are  not?  It  may  be 
that  the  frec|Ucnc\'  of  \oicular  infections  varies  in  direct  proportion  to  the 
degree  of  diligence  in  examining  these  structures. 


)/f«)Ctf 


Fig-.  5.     Ves 


Lewin  and  Daum  examined  1,000  cases  of  gonorrhea,  and  found  the 
posterior  urethra  involved  in  65  per  cent.,  and  the  seminal  vesicles  in  35 
per  cent.  While  there  are  no  statistics  at  hand  to  prove  the  assumption,  it 
seems  reasonable  that  the  vesicles  could  easily  be  infected  from  every  case 
of  chronic  posterior  urethritis,  and  in  many  cases  of  acute  posterior 
urethritis.  If  any  surprise  is  to  be  expressed,  it  is  that  they  escape  in  anv 
case  of  posterior  urethritis. 

W'hen  looking  about  for  "focal  infectious,"  the  vesicles  must  not  be 
overlooked.  Before  having  a  few  hundred'  dollars  worth  of  bridgework 
removed  from  a  patient's  mouth  for  arthritis,  it  would  do  no  harm  to  in- 
vestigate the  vesicles.  The  fact  that  the  patient  states  that  he  has  never 
had  gonorrhea  should  not  deter  one  from  examining  the  vesicles.  He  may 
be  mistaken  or  may  have  forgotten,  besides  a  previous  gonorrheal  infection 
is  not  absolutely  necesary. 

Vesiculitis  may  present  in  men  who  live  under  a  high  nervous  tension, 
who  indulge  in  sexual  excesses  both  normal  and  abnormal,  and  who  are 
intemperate  in  the  use  of  tobacco  and  alcohol.     Horseback  riding,  bicycle 


RAXSOHOFI^-  MEMORIAL  VOLUME 


and  motorcycle  riding  arc  contributing  factors  towarl  the  development  of 
vesicle  trouble. 

Dr.  Robert  T.  Morri.s  has  given  out  for  careful  consideration  and  in- 
vestigation the  suggestion  that  possibly  there  is  some  relation  between  "fo- 
cal infection"  and  malignancy,  even  though  the  malignancy  be  in  some  part 
of  the  body  far  removed  froiu  the  focus  of  infection.  While,  at  first 
thought,  this  may  seem  far-fetched,  yet  it  is  a  study  in  biochemistry,  which 
has  luuch  more  to  commend  it  than  the  suggestion  a  few  years  ago  that 
goitie  and  nianimary  lualignancy  were  produced  by  intestinal  stasis. 

Titbi-rciilosis  of  the  Z'csiclcs  is  i)ractically  always  secondary  to  tuber- 
culosis elsewhere  in  the  genital  tract.  Contrary  to  much  of  the  informa- 
tion formerly  had.  it  was  found  that  vesicles  which  felt  nodular  when  ex- 
amined digitally  per  rectum  are  not  necessarily  the  seat  of  tuberculosis. 
What  was  diagnosed  as  tuberculous  nodules  from  palpation  in  some  speci- 


ig.  0.     iJciiso  tissue  about  vesicles,  vasa  aud  prostate,  result  of  ehronic  intlainniation. 
Left  vesicle  lias  been  dissected   from  its  bed  of  adiiesions 


mens  proxed  to  be  thickened  and  sclerosed  areas  at  the  sharp  angles  of 
the  tubules.  In  one  specimen  a  small  single  nodule,  about  the  size  of  a 
navy  bean,  was  felt  in  the  right  seminal  vesicle.  \\'hen  this  was  dissected 
out  it  was  a  very  firm  and  completely  capsulated  cyst  which  contained  i 
clear  gelatinous  material. 

The  only  cases  of  iiialii/imncy  found  were  secondary  to  malignancy  in  the 
wall  of  the  urinary  bladder.  There  is  no  logical  reason  why  the  vesicles 
should  not  lie  involved  in  jiriniary  malignancy,  and  no  doubt  they  are,  yet 
none  were  found  among  the  specimens  forming  the  basis  of  this  study. 

No  calculi  were  found  in  the  vesicles  among  our  specimens.  They  cer- 
tainly are  not  \ery  common.     Dr.  Eugene  Fuller  informed  me  in  a  per- 


E.  O.  SMITH 


sonal  communication  that  in  the  more  than  seven  hundred  vesiculotomies 
that  he  has  performed  he  found  calcuH  in  only  seven  cases,  and  but  once 
in  both  vesicles  of  the  same  patient. 

There  is  a  case  reported  by  James  and  Shunian  where  a  seminal  vesicle 
calculus  gave  rise  to  the  same  symptoms  as  those  typical  of  renal  colic,  and 
it  was  not  discovered  until  after  a  futile  surgical  search  was  made  for  a 
stone  in  the  ureter.  This  is  an  exceptional  case,  and  an  error  that  anyone 
might  have  made.  However,  with  such  a  case  report  before  us,  we  should 
profit  by  their  experience,  and  ever  keei>  tin's  possibility  in  mind  when  study- 
ing "renal  colic." 

The  points  in  the  study  of  the  anatomy  and  pathology  of  the  seminal 
vesicles  that  seem  worthy  of  special  mention  are : 

(1)  The  wide  variations  in  size  and  positions  of  the  vesicles. 

(2)  Frequency  of  vesiculitis,  both  suppurative  and  inflammatory  ( fo- 
cal infections). 

(3)  The  close  relaticm  of  the  \esicles  to  the  ureters  and  in  some  cases 
to  the  peritoneum. 

(4)  The  futility  of   .severe  massage  treatments. 

(5)  The  importance  of  multiple  incisions  ]\-irticularly  in  the  distal 
portions,  when  surgical  drainage  is  being  done. 

(6)  Palpable  vesicle  nodules  arc  not  always  tuberculous. 


Barnett,    C.    K. :     Patholopy    uf    tlie    Siiniiial     \  .  m.  1,  ,    .ind    Prostate,    with    Suggestions    of    the 
essity    for    Surgical    Treatment.      (J.    Indian. i    .\K    .\--n.    1909.    \'.    2,    pp.    320-J2.) 
Harney.    }.\\:     Observation    ou    the    Seminal    Wsicles.       (Tr,    \m.    .\ssn.    Genito-Urin.    Surg., 

liarney.    I.    I ), :     KiLcnt    Studies   in   the   Patliologv    of    Seminal    \'esicle.s.      (Host.    .M.    and    S.    .1.. 

I,  \-.   171,  |i|.,   -y>-:.2.) 

Bellield,  \V.  r.:  Pus  Tubes  in  tile  Male.  Surgieal  and  Wiceine  Treatment.  (Jour.  .\.  M.  .\.. 
Ceelen,  W. :  Kin  Fibromyom  dor  Snmenhl.isc.  C\'ircho«'s  .\rch.  £.  path,  .\n.lt.,  1912,  \'.  207, 
Felix.    W.:     Zur    .\natomic    des    Duetus    Kjaculatnrius,    der    .\nlpulla    Ductus    Deferenlis    und    der 


Special     K.tMcn.r    t.i     111.      r,,lln yu      iMn.lniu-     ,,i     ihr     l'.,vl,.rini     rrctbr.i.        l\.     \^     -M.     T.,     1913, 

\-.    97,    pp.    0,S2-l,.S-l.) 

James  and  Shuman:  Seminal  \esical  Calculus  Simulating  Nephrolithiasis.  (Surg.,  Gyn.  and 
Obstct.,   xvi,    1913.) 

Junkerman,  C.  K.:  Hematuria  and  the  Pathology  of  Chronic  Seminal  Vesiculitis  and  .\m- 
pullitis  Under  Which  Latter  Disorder  We  Get  Bloody  Semen.  (.Med.  Century,  1911,  V.  18.  pp. 
113-15.) 

Lewin,  A.,  and  Bohm,  G.:  Zur  Pathologic  der  Spermatucvstitis  Gonorrhoica.  (Ztsclir.  f. 
Urol.,   1909,  V.   3.   pp.  M-M.) 

Nussbaum.  M.:  T'eber  .len  Bau  und  die  Tatigkeit  der  Driisen.  \'I.  Der  )!au  und  die 
Cyclischen    XrrandenniLcn    der    Samenblasen    von    Ranafusca.      (.^rch.    f.    mikr.    .Anat..    1912.    V.    80, 

2    .\bt.,     pp      1-^'M 

Ob,  rnd.nf,  ,.  S:  lleilv.it-.  zur  Anatoinie  und  Pathologic  der  Samenblasen.  (Beitr.  t.  path. 
-Knat.    w.    /     .AW.    I'.itli  .    I'.'uJ.    W    31.    pp.    325-40.) 

P.t.  i.Ti.  (I  \  I  i;  :  Ibitr.-iKC  zur  .Mikrokopischen  .\ualoniie  der  W-sicuIa  seminalis  des 
.Menscbrn    mid     Ijihl,,     ^..n. .  I ,.-,  r.       l.\nat..    Mefle,    1907,    \'.    34,    pp.    237-1,2.) 

I.hnnb^.     W      I-    :      Tli,-     .\„al.a.n     .and    Physioloj.y    of    the     Se 
Treatnu.it   .a     Ih,  ,;    l.i-Mnv      il;o-li.n    .\1.   and   S.   J.,    1914,   V. 

Th ;,,  I;  \,  and  Panioast,  II.  K. :  Observation  on  the  Pathology,  Diagnosis  and  Treat- 
ment   (It    Siniinal    \,.„uliti5.      (.\nn.    Surg.,    1914,    V.    60,    pp.    313-18.) 

\'".-l-l-i     illrpl-lberw):     Die    Samenblasen.      1912. 

Weis/.     l-.:      Zn,      .\elioIogie     und     Pathologic     der     Samenblasenerkra.ikungen.       (Wien.     med. 


IXGUIXAL  HERNIA.* 

THE    RELATIVE    TEACHING    VALUE    OF    ACTUAL    PHOTOGRAPHS    AS 
COMPARED  TO  DRAWINGS. 

Chas.  T.  Sm-THEii,  M.D.. 

Cincinnati. 

The  fact  tliat  one  book  on  hernia  has  forty-two  methods  describing 
the  operative  cure  of  inguinal  hernia  and  twenty-seven  methods  describing 
the  cure  of  femoral  hernia,  means  that  many  men  are  either  seeking  to 
have  their  names  apply  to  their  operation  or  there  is  some  fault  to  find 
with  most,  if  not  all  the  methods  yet  devised.  I  am  inclined  to  believe, 
after  rather  extensive  study  of  the  subject,  that  it  is  a  case  of  "straining 
at  a  gnat  and  swallowing  a  camel." 

Proper  application  of  best  known  surgical  principles  to  the  cure  of 
hernia  will  result  in  success  and  cure  of  98  per  cent,  of  the  cases. 

This  paper  is  based  on  seven  years'  careful  study  of  hernia,  from  text- 
books, cadavers,  that  I  ha\e  --een  in  large  clinics,  work  among  my  colleagues 
and  personal  ojierative  experience.  I  was  willing  very  early  in  my  career 
to  concede  that  scientific  o]ierati\e  work  for  the  cure  of  hernia  was  much 
less  common  than  it  should  be.  and  that  hernia  was  one  of  the  difficult  major 
operations  when  considered  from  all  its  standpoints. 

This  is  self-evident  in  the  face  of  the  well-established  fact  that  until  tin- 
last  five  or  ten  years  recurrence  varied  from  5  per  cent,  to  20  per  cent,  in 
the  hands  of  various  operators,  while  at  present  we  can  hope  for  98  per  cent, 
of  cures  to  follow  good  work. 

The  student  must  first  ha\  e  a  perfect  and  complete  knowledge  of  normal 
anatomy  of  the  hernia  region;  he  must  not  only  be  able  to  tell  it.  but  be 
able  to  demonstrate  it  on  both  the  cadaver  and  the  living  subject. 

Secondly,  he  must  be  able  to  recognize  this  same  anatomy  when  the  parts 
are  distorted  by  the  pathological  conditions  found  in  hernia. 

I  do  not  want  to  undervalue  drawings,  but  want  to  try  to  show  that  more 
photographs  in  our  text-books  would  be  a  great  advantage  in  imparting  to 
students  (under  and  post-graduate)  the  knowledge  necessary  for  them  to 
have  to  enable  them  to  do  a  hernia  operation  in  a  scientific,  anatomic  and 
curative  way. 

-Any  surgical  condition  that  is  sf)  cimimon  that  it  can  be  found  in  6  per 
cent,  of  the  male  ])n])ulation  and  in  2  per  cent,  of  the  female  population  de- 
serves the  most  careful  possible  teaching.  Further,  a  very  small  per  cent, 
of  students  leaving  college  are  able  to  do  a  hernia  operation  properly,  and 
they  usually  get  less  able  as  they  grow  older,  unless  they  have  hospital  train- 
ing or  work  as  an  assistant  to  some  capable  surgeon.    The  simple  relief  of 


Mississippi    VaMey    -Medical    .\ssociatic 
■Clinic,    rcbniarv    11,    19U. 


CHAS.  T.  SOUTHER 


'J 


Drawings  reproduced  from  Ferguson's  Book 
on  Hernia.  1906.  Diagrammatic,  showing  points 
at  which  different  forms  of  hernia  push 
through;  looking  out  from  within  the  abdomen. 


PLATE  2. 
Di>>section    to    show    location    of    incision 
aponeurosis  of  the  external  oblique,  having  tl 
external     ring    intact    as    a    landmark.       Coi 
coming  out  through  external  ring.     Separatic 
of  fibers  of  external  oblique  beginning  above. 


strangulated  hernia  as  an  emergency  is  not  saying  a  man  really  knew  what 
he  did,  except  to  replace  the  gut. 

Incision  for  hernia  includes  (1)  the  inci.sion  through  the  skin,  fat  and 
sujjerticial  fascia;  (2)  aponeurosis  of  external  oblique.  The  direction  and 
location  of  these  two  cuts  means  much.  Skin  and  fat  should  preferably 
be  lifted  up  and  either  cut  with  scissors  or  transfixed  with  a  pointed  knife, 
so  as  not  to  wound  the  aponeurosis  of  the  external  oblique  at  a  point  that 
is  not  desirable.  The  external  incision  should  be  located  in  the  folds  of  the 
groin  and  be  ample  in  length.  Dr.  Wm.  Mayo  often  makes  the  assertion 
in  his  teachings  that  skin  and  fat  are  only  coverings,  and  limited  only  by 


I   of   specimen   showinj 
vessels,  ilioinguinal  ne 


PL.\TE 
'ing   knot    of    suture 


RANSOHOFF  MEMORIAL  VOLUME 


PLATE  5. 

deferens  as  it  passes  behi 


;   cord   rcfle 
internal    oblique    shi 


ard;   deep   epigas- 


tlie  contents  within.     !n  other  words,  the  skin  and  fat  tissues  have  no  re- 
tentive or  curative  influence  in  the  oiieration  for  hernia. 

The  incision  in  the  external  obhque  muscle  or  aponeurosis  can  be  made 
from  helow  up  or  from  above  down  (  Bodine  and  Judd)  and  far  enough 
from  Poupart's  hgament  to  allow  of  whatever  amount  of  overlapping  may 
be  indicated  in  the  given  case.  The  rule  is  to  divide  this  aponeurosis  half 
way  between  Poupart's  ligament  and  the  rectus  muscle  or  linear  semi- 
lunaris; the  external  ring  can  be  left  intact.  This  overlapping  causes  the 
strain  to  I)e  taken  off  the  internal  oblique  sutures,  and  allows  more  perfect 


M 


^ 


A 


ing  external   obi 

que   incision,   dir 

ection 

of   nni^ 

cle   fibers  of   inte 

rnal   oblique,   sac 
transfixed,   cord. 

with 

neck    li 

sated   and   being 

deep 

ep.gast 

uter   pillar   of  ex 

ernal 

Ferguson  operation,  from  his  boo 
ing  cremaster  muscle  to  traiisversalis 
drawing  by  Miss  Cleveland. 


CHAS.  T.  SOUTHER 


union  with  the  internal  obhque  and  (he  deeper  structures  of  the  canal, 
meaning  cord  and  transversalis  fascia  and  pedtoneum. 

Plate  1  is  extremely  important  in  enal)ling  the  student  to  diagnose  the 
\ariety  of  hernia  with  wliieh  lie  has  to  deal,  and  is  probably  more  illustra- 
tive in  a  way  than  an  actual  dissection  cmild  be  made.  It  is.  therefore,  one 
point  in  favor  of  drawings. 

Plate  2  shows  skin  incision  of  ample  proportions,  a  little  larger  than 
necessary,  except  to  get  a  good  ])lintograph.  Skin  and  fat  are  reflected  be- 
low   Poupart's   ligament   and   ahoxe   to   linea   semilunaris,   giving   full    view 


hernia;  (1)  Double  arrow,  external  oblique  reflected;  (3)  internal 
oblique;  (3)  cord;  (1)  deep  epigastric  vessels;  (.'">)  neck  of  sac 
ligaled.  ready  to  be  transfixed.  White  lines  on  internal  oblique 
show  direction  of  muscle  fibers. 

of  the  entire  hernia  region  and  greatly  facilitates  identification  of  anatomi- 
cal structures,  making  the  operation  easier  and  more  quickly  accomplished. 
It  also  shows  the  location  of  incision,  or  rather  the  point  at  which  the 
fibers  of  the  aponeurosis  of  the  external  oblique  are  separated,  beginning 
above  and  going  down  to  the  semi-circular  fibers  that  form  the  external 
ring.  These  ring  fibers  may  or  may  not  be  cut,  or  they  may  be  stretched 
out  and  nearly  or  quite  obliterated  in  large  scrotal  hernise.  In  a  small  her- 
nia don't  cut ;  in  large  hernia  better  cut  and  overlap  for  support. 

If  we  leave  a  large  leaf  in  the  lower  flap  of  external  oblique  aponeurosis, 
we  can  gras])  it  with  small  forceps  or  rubber-covered  clamps,  and  wipe  off 
(with  gauze)    the  under  surface  of   the  riponcurosis  and  expose    (without 


RANSOHOFF  MEMORIAL  VOLUME 


PLATE  11. 

iction  of  drawing  from  Fergu 
A'ing  Basini  operation,  with  int 
itched  to  Poupart's  ligament : 
iture  used. 


effort)  the  shelving  edge  of  Poupart's  ligament,  an  early  and  very  im- 
portant step  in  both  the  Bassini  and  Ferguson  operations. 

This  usually  takes  us  down  to  the  cord,  and  the  sac  will  usually  be 
found  (in  a  small  hernia)  above  and  slightly  internal  to  the  cord.  That 
is,  the  sac  is  next  to  the  conjoined  tendon,  and  the  cord  is  ne.xt  to  the  shelv- 
ing edge  of  Poupart's  ligament,  all  usually  receiving  a  ciiveriiig  from  the 
cremaster  muscle. 

Plate  3  shows  external  oblique  reflected,  ilio-inguinal  nerve  passing  over 
forceps  lengthwise  and  cord  reflected  inward  to  show  location  of  shelving 
edge  of  Poupart's  ligament.  Passing  transversely  over  the  jaws  of  the  for- 
ceps are  the  deep  ejiigastric  vessels  and  sheath  ligated.     Fibers  of  external 


PLATE  12. 

l"eigu> 

)peration. 

from    his 

book 

printed 

OchsnerS 

••Clinical 

.Sn 

Suturing 

inter 

lal  oblique 

s    llg 

Drawing 

bv  A 

S.  Clevel 

Pane  .;.). 

CHAS.  T.  S(U  I HFR 


PLATE  15. 
Suture  knot  seen  in  internal  oblique  is  same 
lat  ligated  and  transfixed  the  neck  of  the  sac. 
[uscle  suture  is  Ferguson's  continuous  method. 


ring  are  intact.  Internal  oblique  muscle  is  here  exposed  to  a  greater  extent 
than  necessary  in  operation. 

Plate  4.  Anatomical,  same  as  Plate  3,  with  cord  reflected  down  and 
out,  deep  ves.sels  up  on  forceps.  Sac  of  hernia  has  been  ligated  and  trans- 
fixed well  up  under  internal  oblique  muscle,  as  shown  by  knot  of  thread, 
which  shows  well  up  on  surface  of  internal  oblique. 

Plate  5.  I  do  not  think  I  have  ever  seen  a  plate  that  demonstrates  so 
perfectly  the  point  at  which  the  vas  deferens  passes  with  cord  over  the 
deep  epigastric  vessels.  This  is  important  as  regards  suturing  the  cremas- 
teric muscle  to  internal  oblique,  as  advised  by  Ferguson. 

The  relative  retentive  power  and  influence  of  the  cremaster  muscle  on 
the  cure  of  hernia  depends  on  the  (1)  method  of  operation  and  (2)  on  the 


A 


ply  approximated 


PL.\TE  17. 
lead's    operation    from    Fergus* 
>     tied     are     holding     creniaste 
internal  oblique. 


Page  5.« 


RAXSOHOFF  MEMORIAL  VOLUME 


size  or  development  of  the  muscle  itself.  The  cremaster  forms  (with  its 
fascia)  one  of  the  coverings  of  the  sac,  while  it  passes  through  the  inguinal 
canal.  By  opening  this  sac  and  careful  preservation  of  the  cremaster  it 
can  be  used  to  cover  over  the  cord  and  attach  to  the  under  side  of  the  con- 
joined tendon  and  internal  oblique  (Halstead).  In  this  method  it  forms 
the  first  step  in  the  suture  part  of  the  operation. 

It  is  impracticable  to  use  it  in  a  Bassini  operation  or  in  cases  where 
the  muscle  is  deficient  in  development,  and  has  little  or  no  retentive  power. 

The  amount  of  importance  given  to  this  muscle  by  Halstead  and  Fer- 
guson and  others  make  us  give  it  a  certain  definite  place  in  the  technique. 


PLATE  IS. 

(ive  interrupted  sutui  es  parsed  through 
lined    tendon,    under   shelving   edge    of 

both  ends  passed  through  external 
all  knots  above  external  oblique  fascia 

canal.      Modified   Ferguson   operation 


Plate  6  gives  best  view  of  shelving  edge  of  Poupart's  ligament,  with 
cord  displaced  inward. 

Plate  7  shows  method  of  ligation  and  transfixion  of  the  sac.  which  is 
believed  by  a  number  of  authorities  to  he  a  very  important  and  essential 
step  in  the  operation. 

Plate  8  is  a  drawing  by  a  splendid  artist  and  from  Ferguson's  book. 
It  was  unforunate,  in  the  opinion  of  the  writer,  to  have  so  splendid  a  book 
as  Ferguson's  work  on  hernia  so  ])rofusely  illustrated,  and  not  have  a 
single  photograph  in  the  entire  book. 

Page   5.!', 


CHAS.  r.  SOUTHER 


Plate  8  speaks  for  itself,  and  for  comparison  Plate  10  (my  own  photo) 
is  intended  to  illustrate  what  the  real  operation  looks  like. 

Plate  9  is  the  key  to  all  the  photos  and  is  intended  only  to  aid  the  under- 
graduate student. 

Plates  11,  12  and  13  are  rejjroductions  of  draii'iiu/s  from  Ferguson's 
book  and  are  described  under  each  cut. 

Plates  16  and  18  are  illustrative  of  what  seems  to  me  an  advantage  in 
placing  the  sutures  holding  the  internal  oblique  {conjoined  tendon)  over  to 
Poupart's  ligament.  These  sutures  are  placed  as  mattress  sutures,  begin- 
ning by  passing  the  round-pointed  half  curved  needle  from  without  through 
the  lower  flap  of  external  oblique  aponeurosis  just  above  Poupart's  liga- 
ment, then  from  without  in  through  internal  oblique  (conjoined  tendon), 
while  the  same  is  held  upon  finger,  then  from  within,  out  under  Poupart's 


PL.XTE  19. 
Drawing  by  A.  S.  Cleveland. 
D   show   HaLstead   technique,    i 
f    rectus    when    internal    oblii 
'rom  Ferguson's  book. 


ler   M.  lirodel. 


PIRATE   20. 

Showing  three  rows  of  sutui 

oblique  fascia  overlapped  the 

second  and  third  row  of  sutur: 


ligament,  coming  out  on  top  of  the  lower  flap  of  aponeurosis  of  external 
oblique   fascia. 

Overlapping  the  External  Oblique  Fascia. — This  can  always  be  done, 
provided  the  primary  incision  is  properly  placed,  namely,  midway  between 
Poupart's  ligament  and  the  linea  semilunaris.  When  the  external  oblique 
fascia  is  overlapped  (see  Plates  20  and  21),  it  takes  up  the  surplus  in  the 
tissues,  and  by  putting  more  tension  on  fascia  causes  the  linea  semilunaris 
to  be  drawn  nearer  Poupart's  ligament  and  relieves  tension  on  internal 
oblique  and  conjoined  tendon,  thereby  facilitating  union  of  the  deeper  struc- 
tures. This  carries  out  the  most  accepted  surgical  principles  advocated  by 
the  best  authorities  in  the  treatment  of  all  forms  of  ventral  hernia,  namely, 
overlapping  the  fascia. 

Suture  Material. — Consensus  of  opinion  among  the  big  operators  is  so 
greatly  in   favor  of  animal  ligature  that  wire,   silk,   linen  and  silk   worm 

Page   Mr, 


RANSOHOFF  MEMORIAL  VOLUME 


gut  will  not  be  considered.  The  opinion  of  Coley,  Ferguson,  Judd  and  the 
late  W.  T.  Bull  must  be  accepted  until  disproved,  and  they  all  use  catgut, 
some  chroniicized.  some  plain.  Most  of  them  favor  a  twenty  or  thirty 
dry  chromic  gut,  never  larger  than  a  No.  2,  and  Ferguson  favors  No.  1. 
Interrupted  sutures  have  the  greatest  number  of  advocates. 

'I'hree  knots  should  be  put  on  each  of  the  deep  sutures,  including  muscle 
and  Pouparl's  ligament.  For  lapping  the  fascia  No.  0  chromic  gut  may 
be  used.     A  heavier  plain  or  iodin  gut  has  many  advocates. 

Never  put  a  tension  on  sutures,  and  never  tic  tight  enough  to  obstruct 
the  blood  supply.  , 

Suppuration  is  constantly  jiresent  in  all  wounds  where  sutures  are  tied 
tight  enough  to  stnp  ibc  blood  supjily.     Tissues  zcill  die  :^'hen  strangled. 


1  belie\e  that  more  returns  and  more  infected  wounds  in  hernise  are 
due  to  putting  the  sutures  too  tight  than  all  other  causes  combined.  This 
is  particularly  true  of  the  skin  suture.  Some  form  of  non-absorbable  suture 
is  best  for  the  skin,  but  should  be  removed  from  fifth  to  tenth  day.  How- 
ever, if  there  is  no  tension  and  tissues  are  carefully  approximated  with  silk 
worm  gut,  silk  or  linen,  either  by  subcuticular  stich  or  Glover  stitch,  the 
suture  material  will  do  no  harm  for  ten  days.  However,  the  skin  suture 
has  done  all  the  good  one  can  hope  for  in  six  days,  and  union  will  be  more 
rapid  if  it  is  removed  at  this  time. 

It  is  claimed  by  many  that  a  double  strand  of  No.  1  chromic  catgut  is 
preferable  to  a  heavier  suture  material,  used  single. 

']'he  present  tendency  is  all  toward  the  smallest  possible  ligature  that 
will  hold,  and  No.  1  has  been  ample  for  most  operators.  Personally  I  have 
used  nothing  heavier  than  No.  2  for  any  kind  of  work  for  years. 

Page  536 


CHAS.  r.  SOUTHER 


In  order  to  tie  the  knot  tightly  and  not  strangulate  the  tissues,  make 
the  first  knot  easy  or  loose,  and  then  insert  the  point  of  artery  clamp  under 
the  knot,  and  tie  second  and  third  knot  as  tight  as  suture  will  stand,  then 
remove  the  force])s,  and  tissues  will  not  be  strangulated. 

The  writer  has  favored  the  antamic  operation  of  Ferguson  for  several 
years,  l)ut  has  been  perfectly  willing  to  give  equal  merit  to  Rassini's  method 
on  account  of  the  large  number  of  operators  who  favor  it.  Bull  and  Coley 
and  others  are  warm  advocates  of  Bassini's  method. 

If  the  student  will  study  Coley 's  and  Ferguson's  writings,  and  take  the 
liberty  to  read  a  little  between  the  lines,  he  will  see  that  they  do  not  differ 
greatly.  Coley  calls  it  Bassini's  operation  with  or  without  transplantation 
of  the  cord.  Coley's  writings  have  been  more  especially  of  hernia  in  child- 
hood, at  which  time  cure  is  less  difficult. 

Disposition  of  the  Sac  in  Hernia. — Quoting  from  a  recent  paper  on  this 
subject  (C.  T.  S.,  Lancci-Climc.  October  6,  1909,  Deansley,  British  Medical 
Journal).  I  believe  that  effectually  removing  the  sac  cures  95  per  cent,  of 
cases  of  hernia. 

Macewen  lays  great  stress  on  complete  removal  of  sac  by  ligation  and 
transfixion  under  internal  oblique  (Plate  7). 

Ball  (by  Ferguson)  removes  the  sac  alone  in  children,  and  says  sutures 
are  i.ot  necessary  'mless  cough  is  present. 

Colev  says  the  sac  is  largely  congenital,  and  its  removal  is  best  in  all 
v-ases 

Ferguson  says  the  congenital  deficiency  in  the  internal  oblique  plays  an 
important  part  in  the  etiology,  but  he  always  removes  the  sac. 

The  consensus  of  opinion  from  the  recognized  authorities  on  hernia 
may  be  taken  in  abstract  as  follows:  Hernia  has  a  complete  sac  except  in 
the  sliding  form,  which  is  rare,  but  should  be  borne  in  mind  always. 

Removal  of  the  Sac  by  .'iutitre.  Ligature  or  Obliteration. — Sellenings 
(American  Journal  of  Surgery.  March.  1909)  claims  to  have  gotten  his 
idea  from  Matta's  treatment  of  aneurismal  sac  obliteration.  It  has  been 
settled  beyond  a  question  of  doubt  that  a  peritoneal  lined  sac  can  be  trans- 
formed into  fibrous  connective  tissue  by  proper  treatment.  Nature  proves 
this  by  the  fact  that  we  all  do  not  have  hernial  sacs.  R.  C.  Coffee  and 
others  have  been  instrumental  in  bringing  out  the  clinical  proof  of  same ; 
yet  removal  and  ligation  with  or  without  transfixion  is  the  most  accepted 
'method  today.  So  important  is  this  care  of  the  sac  that  in  femoral  hernia 
(small  variety)  removal  of  the  sac  with  its  proper  transfixion  will  cure 
hernia  of  the  femoral  type,  even  though  we  do  not  close  the  femoral  canal 
(Ochsner). 

This  same  assertion  holds  good  in  the  treatment  of  inguinal  hernia  of 
early  childhood,  prior  to  five  years  (Ball  and  E.  K.  Herring). 

The  transfixion  of  the  neck  of  the  sac  is  advocated  by  Macewen,  Butler, 
Halstead,  Ferguson,  Lanphear  and  others ;  yet  in  the  light  of  the  role  it 


RAXSOHOFF  MEMORIAL  J-QLUME 


plays  in  femoral  hernia,  I  do  not  believe  it  has  been  sufficiently  emphasized. 
Treating  the  stump  by  this  method  changes  the  point  of  greatest  intra- 
abdominal pressure  and  greatly  facilitates  cure.  It  removes  the  infundi- 
buliform  process  of  peritoneum  and  prevents  a  continuation  of  the  intra- 
abdominal pressure  at  this  point  by  obliterating  the  depression  at  the  in- 
ternal ring. 

The  probability  of  hydrocele  developing  is  greater  with  Bassini's  opera- 
tion than  with  Ferguson's.  \Mien  the  distal  portion  of  the  sac  is  left 
undisturbed,  the  upper  end  where  it  has  been  severed  from  the  neck  .should 
be  anchored  with  small,  plain  catgut  to  the  cord,  and  never  ligated.  This 
prevents  formation  of  hydrocele  to  a  great  extent. 

My  own  impression  and  practice  has  been  to  ligate  at  neck,  well  up 
under  distal  border  of  internal  ring,  and  cut  off.  The  distal  portion  of  sac 
may  be  removed  if  the  hernia  is  acquired.  Distal  portion  may  be  left  in 
position  when  hernia  is  congenital,  that  is,  when  sac  is  continuous  with 
the  tunica  vaginalis  testis.  This  point  should  be  determined  at  once  when 
the  sac  is  opened,  and  treatment  instituted  accordingly.  The  abo\e  is  sub- 
ject to  some  modification  when  sac  is  large,  thick  and  old.  and  it  may  be 
treated  as  individual  operator  likes. 

In  further  consideration  of  congenital  hernia  sac  is  best  treated  by 
Doyen  or  Bottle's  operation  for  hydrocele.  ( Recently  published  as  new  by 
E.  \\".  Andrews,  Chicago,  Annals  of  Surgery,  1909.)  Simple  eversion 
around  the  testicle  and  one  stitch  put  at  the  top ;  this  absolutely  cures  and 
prevents  any  possible  formation  of  liydrocele  without  the  time-consuming 
element  of  removal. 

I  always  transfix  the  ligated  neck  of  sac  up  under  internal  oblique 
muscle. 

Contents  of  sac  can  be  returned  to  abdominal  cavity  in  all  simple  un- 
complicated cases. 

Resection  of  intestine  and  excision  of  incarcerated  omentum  are  at 
times  necessary  in  strangulated  forms  of  hernia,  but  can  not  be  treated 
here.  A  good  way  to  test  the  re-establishment  of  the  circulation  is  to  re- 
place a  doubtful  piece  of  gut  into  the  cavity  after  ha\ing  passed  a  heavy 
long  suture  through  the  mesentery  under  the  gut.  so  the  same  gut  can  be 
reinspected  before  closing  the  hernia.  This  relief  of  tension  is  frequently 
followed  by  a  return  of  the  color  and  normal  circulation.  When  the  gut 
can  not  be  replaced  without  undue  pressure  it  is  best  to  enlarge  the  ring, 
or  make  a  second  incision  above  and  pull  the  gut  back  from  within  the 
cavity  in  femoral  hernia. 

Charles  Harrison  Frazier,  of  Philadelphia  (Annals  of  Surgery,  Octo- 
ber, 1911,  p.  555),  shows  the  only  cut  I  have  ever  seen  illustrating  the  mat- 

Page  S3S 


CHAS.  T.  SOUTHER 


tress  suture  for  the  interal  oblique  and  Poupart's  ligament  and  external 
aponeurosis  which  advocates  the  tying  of  the  sutures  all  external  to  ex- 
ternal oblique.  This  was  published  after  the  completion  of  this  paper. 
Rose  and  Carless  "Manual  of  Surgery."  1907.  contains  a  cut  illustrating 
what  Frazier  brought  out,  but  no  emphasis  is  put  on  it  in  the  text. 

1  have  tried  to  understand  what  the  other  fellow  has  tried  to  teach,  and 
have  tried  to  present  the  advantage  that  the  photograph  has  over  the  draw- 
ing, or  at  least  that  it  should  have  a  more  prominent  place  in  the  teaching 
of  hernia  than  it  has  formerly  occupied. 


TOXICITY  (IF  URINE  IN  PREGNANCY.* 


rr  W.  Stkw. 
Ci 


In  the  year  1897  the  writer  made,  with  tlie  urine  of  pregnant  women,  i 
numlier  of  experiments  on  rabbits  with  the  object  of  determining  the  toxicity 
of  such  urine.  The  great  variabihty  in  results  which  \'o!hard'  had  obtained 
when  going  over  the  work  of  Ludwig  and  Savor,-  Tarnier  and  Chambre- 
lent,^  Bouchard^  and  others  seemed  to  justify  the  conchision  that  the  in- 
travenous injection  into  the  circulation  of  so  foreign  a  fluid  as  urine  was 
open  to  grave  objection,  especially  as  Volhard  found  numerous  cases  in 
which  thrombosis  was  a  decided  contributing  factor,  if  not  tlie  principal  one, 
in  the  production  of  death.  The  writer's  experiments  were  made  with  urine 
which  had  been  collected  under  what  was  supposed  to  be  careful  asepsis, 
over  boric  acid.  This  urine  was  concentrated,  filtered,  neutralized  and  in- 
jected warm  into  the  abdominal  cavities  of  rabbits,  in  tlie  proportion  of  80 
to  100  c.cm.  to  kilogramme  of  animal.  The  following  experiment  shows 
the  character  of  the  work  done : 

"Experiment  VII — May  13,  1897. — Urine  of  a  primipara  (Kramig) 
aged  twentv-one  years.  Specific  gravity.  1,01.");  acid;  no  albiunin ;  no  sugar. 
Woman  always  healthy ;  well  developed ;  date  of  expected  confinement.  June 
29,  1897.  Family  history :  Father  died  of  heart  disease ;  mother  healthy. 
No  diathetic  condition  discoverable.  This  urine  was  boiled  down  to  one- 
third  of  its  bulk,  to  specific  gravity,  1,056;  fifty  cubic  centimeters  of  this 
concentrated  urine  were  neutralized,  filtered,  warmed  and  injected  into  ab- 
domen of  a  rabbit  weighing  1,750  grammes,  in  fifteen  minutes.  4:00  p.  m., 
returned  to  cage ;  can  not  support  himself ;  lies  flat  on  abdomen ;  makes 
effort  to  regain  his  feet;  respiration  slow;  supports  head  against  side  of 
cage.  4  :07  p.  m.,  has  convulsion,  tonic  followed  by  clonic  spasms,  opisthot- 
onos ;  pupils  contracting ;  breathing  in  short  gasps ;  lies  on  side ;  can  not  be 
arou.sed;  palpabral  reflex  absent.  4:10  p.m.,  stretches  himself  every  thirty 
seconds  (about)  ;  these  attacks  are  undoubtedly  convulsive;  during  interval 
is  quiet.  4:18  p.m.,  attacks  come  on  regularly  and  are  accompanied  by  a 
peculiar  grunting  sound.  4  :24  p.  m.,  the  last  attack  was  of  longer  duration 
than  the  others ;  the  abdominal  muscles  are  contracted ;  the  front  and  hind 
legs  are  drawn  together ;  the  fore  legs  tremble  while  the  hind  ones  move 
up  and  down.  4:28  p.m.,  panting;  mouth  open;  stretching  precedes  the 
convulsive  attacks,  which  are  becoming  more  marked.  4:30  p.m.,  violent 
convulsion ;  death. 

"Post-mortem  examination,  eight  hours  after  death;  fifty-five  cubic  cen- 
timeters of  amber  fluid  of  specific  gravity  of  1,022  found  in  abdominal  cav- 


ROBERT  JV.  STEWART 


ity;  abdominal  vessels  injected;  organs  normal  in  appearance;  post-mortem 
discoloration  of  abdominal  wall  on  left  side."" 

The  convulsions  which  are  described  were  found  in  almost  every  case, 
and  simulated  so  closely  the  convulsions  of  strychnia  poisoning  or  of  puer- 
peral eclampsia  that  there  seemed  to  be  no  reasonable  doubt  that  the  urine 
of  pregnancy  contained  deadly  poison  or  poisons,  and  that  the  method  of 
injection  made  no  appreciable  difference.  It  seemed  further  justifiable  to 
conclude  that  the  poison  was  very  soluble,  was  not  aft'ected  by  heat,  and  that 
it  was  a  constant  ingredient  of  the  urine,  because  the  mortality  was  100 
per  cent. 

During  the  year  1897,  after  the  results  of  the  foregoing  experiments 
liad  been  published,  new  experiments  were  made  under  the  same  methods, 
brt  upon  both  rabbits  and  white  mice.  The  urine  was  used  concentrated  and 
unconcentrated.  "The  mortality  was  again  nearly  100  per  cent.  The  figures 
are  as  follows :  Unconcentrated  urine  taken  during  the  last  month  of  preg- 
nancy killed  seven  rabbits  and  two  mice,  one  mouse  recovered;  when  con- 
centrated it  killed  two  mice  and  failed  with  one ;  when  taken  during  labor, 
unconcentrated  urine  killed  one  rabbit  and  one  mouse,  and  spared  none ; 
when  taken  post-partum,  the  unconcentrated  killed  two  rabbits  and  one 
mouse,  and  failed  with  none."" 

The  method  seemed  good  for  rabbits  and  white  mice,  and  no  difference 
could  be  detected  between  concentrated  and  unconcentrated  urine.  At  this 
juncture,  1898,  Dr.  F.  Forchheimer  suggested  that  we  carry  on  a  new  line 
of  work,  the  urine  to  be  taken  not  only  from  pregnant  women,  but  also 
from  patients  who  were  suffering  from  various  forms  of  intestinal  auto- 
intoxication. The  results  of  this  joint  work  were  published  in  the  American 
Journal  of  Medical  Sciences,  September,  1899.  The  special  work  which 
the  writer  did  in  connection  with  Dr.  Forchheimer  was  published,  together 
with  .some  new  experiments,  in  the  American  Journal  of  Obstetrics.  \'ol.  XI. 
No.  3,  September,  1899.  The  mortality  in  this  special  work  agreed  so  closely 
with  that  in  our  joint  work  that  the  writer  can  show  what  that  work  was  l)y 
quoting  from  his  own  paper. 

"The  method  in  detail  was  as  follows :  Women  were  to  Ijc  near  term  ; 
the  genitals  to  be  thoroughly  cleansed  with  soap  and  water ;  the  urine  to  b'.' 
drawn  by  sterile  catheter  into  sterile  Erlenmyer  flasks,  which  were  cotton- 
stoppered  before  and  after  filling;  the  urine  to  be  immediately  boiled  and 
then  sent  to  our  laboratory  and  injected  (this  was  usually  done  at  once, 
sometimes  twelve  or  more  hours  later)  ;  injections  to  be  made  intra-abdomi- 
nally  under  same  precautions  as  heretofore,  except  that  the  urine  was  neither 
neutralized  nor  filtered.  Experiments  were  made  on  six  rabbits  and  twelve 
mice  with  urine  taken  from  eight  women.  The  proportions  used  were 
about  the  same  as  those  of  the  previous  experiments  (80  to  100  cubic  cen- 
timeters to  kilo)  ;  a  mouse  received  25  minims,  as  a  rule,  but  in  four  in- 
stances 50  minims  were  injected  into  these  animals.     All  of   the  animals 

P^gc   o'll 


RAXSOHOFF  MFMORIAL  VOLUME 


lived  except  one  mouse,  which  had  received  50  minims ;  it  died  in  twenty- 
four  hours.  The  mortahty  was,  therefore:  Rabbits,  nothing;  mice,  8  per 
cent.  In  addition  to  these,  four  other  experiments  were  made  on  mice 
with  urine  taken  from  women  in  labor,  and  one  with  that  of  the  post-par- 
tum  period.  All  of  these  mice  recovered.  Three  other  animals,  one  rab- 
bit and  two  mice,  received  injections  of  urine  which  was  twenty-four  hours 
old;  all  died.  If  these  experiments  be  grouped  in  classes,  it  will  be  found 
that  of  urine  boiled  at  once  and  used  within  twenty-four  hours  the  figures 
stand:  Seven  rabbits  and  nineteen  mice  experimented  upon,  of  which  six 
rabbits  and  sixteen  mice  recovered,  a  mortality  of  rabbits,  15  per  cent:; 
mice,  16  per  cent.;  all  animals  together,  15-(-  per  cent.  Mortality  after 
urine  has  stood  for  twenty-four  hours,   100  per  cent."" 

The  new  experiments  to  which  reference  has  been  made  were  made  to 
test  this  method.  As  stated  in  that  paper,  "I  used  unconcentrated  urine 
from  seven  women,  the  majority  of  whom  were  in  the  last  month  of  preg- 
nancy, the  others  in  the  post-partum  period.  The  results  show  that  fresh, 
unboiled  urine  killed  one  mouse  out  of  five,  or  20  per  cent.:  while  fresh 
boiled  urine  killed  two  mice  out  of  nine,  or  22  per  cent. ;  that  the  same 
unboiled  urine,  after  standing  for  twenty-four  hours,  in  cotton-stoppered, 
sterile  flasks,  killed  all  five  of  the  mice,  or  100  per  cent. ;  while  boiled  urine 
which  had  stood  for  twenty-four  hours  in  similar  flasks  killed  four  out  of 
five  mice,  or  SO  per  cent." 

The  experiments  of  the  early  part  of  1859  agreed  with  those  of  Dr. 
Forchheimer's  so  closely  in  regard  to  mortality  that  there  was  good  reason 
to  believe  that  some  carelessness  in  the  collection  of  the  urine  must  have 
caused  the  increased  mortality  in  the  experiments  which  are  quoted  in  the 
preceding  paragraph.  The  writer  decided  to  again  test  the  question,  and 
to  include,  at  Dr.  Forchheimer's  suggestion,  the  question  of  the  probable 
action  of  bacteria  in  the  production  of  the  poisonous  substances  which 
were  evidently  in  the  urine.  In  accordance  with  this  decision  and  sugges- 
tion, a  new  line  of  experiments  was  begun  in  the  early  months  of  1900. 
The  method  was  along  the  lines  pursued  in  the  more  recent  work,  but  dif- 
fered not  only  in  the  greater  care  which  was  used,  but  also  in  the  particu- 
lars which  are  mentioned  below.  The  details  are :  The  urine  was  drawn 
ofl^  by  means  of  sterile  catheters  into  sterile  cotton-stoppered  Erlenmyer 
flasks  at  about  se\en  o'clock  in  the  morning,  the  external  genitals  of  tho 
patient  having  previously  been  carefully  scrubbed  with  soap  and  water, 
then  bathed  in  lysol  solution  (dr.  1  to  Ol).  and  finally  washed  off  with 
sterile  water.  Especial  care  was  given  to  the  meatus  urinarius.  Stress  was 
laid  upon  the  instruction  that  the  urine  was  to  be  the  accumulation  of  the 
night  as  nearly  as  possible.  Only  one  catheterization  was  permitted,  and 
the  urine  was  drawn  oft'  in  nearly  equal  quantities  into  two  flasks,  the  con- 
tents of  one  of  which  were  to  be  immediately  boiled.  The  urine  was  taken 
from  pregnant  and   puer])cral   women.     This  urine  was   injected  intra-ab- 


ROBERT  IV.  STEWART 


dominally  into  white  mice  in  quantities  of  from  fifteen  to  twenty-five 
minims  to  the  animal.  The  greatest  care  was  demanded  that  surgical  asep- 
sis be  observed  in  all  manipulations.  An  ordinary  hypodermic  syringe 
was  used,  the  needle  of  which  was  pointed  downwards  to  avoid  wounding 
liver,  heart  or  other  organ.  Boiled  and  unboiled  urine  was  injected  into 
individual  mice  on  the  first,  second  and  fourth  days,  or  more  definitely 
within  twelve,  thirty-six  and  eighty-four  hours  of  the  catheterization.  At 
the  time  of  making  the  injections,  plate  cultures  were  made  on  gelatin  or 
agar-agar. 

Nine  series,  or  forty-eight  experiments  in  all,  were  made  with  urine 
taken  from  seven  women.  In  seven  of  the  series  the  urine  was  taken  dur- 
ing the  last  month  of  pregnancy,  and  in  two  from  the  i)ost-partum  period. 
The  women  were  all  healthy,  never  showed  any  symptoms  of  eclampsia, 
nor  any  evidences  of  kidney  or  bladder  trouble. 

Forty-eight  mice  were  used.  Forty  recovered  and  eight  died.  Of  the 
eight,  six  died  after  injections  of  unboiled,  and  two  after  boiled  urine. 
The  two  last-mentioned  mice  probably  died  from  causes  which  had  noth- 
ing to  do  with  any  poisonous  properties  which  the  urine  may  have  pos- 
sessed. One  died  in  five  days,  undoubtedly  from  asphyxia,  as  its  air  supply 
was  cut  oflf  by  the  inadvertent  covering  of  the  jar  in  which  the  animal 
was  confined ;  the  other  died  in  ten  minutes  without  convulsive  action, 
probably  from  injury  to  some  organ.  These  probabilities  are  strengthened 
by  the  fact  that  unboiled  urine  from  the  same  catheterization  and  used  at 
the  same  time  did  not  kill  the  mouse.  This  explanation  is  made  because 
if  these  two  mice  be  included  in  the  tables,  the  mortality  rate  is  16%  per 
cent,  (eight  in  forty-eight),  while  if  they  be  excluded,  the  rate  js  reduced 
to  13  per  cent.  +  (six  in  forty-six).  With  this  explanation  it  is  thought 
best  to  include  the  animals  referred  to  in  all  subsequent  deductions.  The 
details  of  the  mortality  are  shown  in  the  following  tables : 


Unboiled 

I-IUST   U.W   UKINIC 

(3  to  12  hours) 

Re 

covered 
8 

5 
7 

5 
S 

Died 
1 

Boiled    .  . 

^  C  '-""1 

Unboiled    

SECOND    IMV    URINE 

(27  to  36  hours) 

2 

Boiled   

0 

Unboiled    .  . 

fOUKTU    DAY    URINE 

(75  to  84  hours) 

^ 

Boiled   

0 

RAXSOHOFF  MEMORIAL  VOLUME 


If  the  position  which  was  taken  in  reference  to  the  two  mice  that  died 
after  injections  of  boiled  urine  be  tenable,  the  mortality  from  boiled  urine 
was  nothing,  while  that  from  unboiled  urine  was:  First  day.  11  per  cent.; 
.second  day,  28.6  per  cent.;  fourth  day,  37.5  per  cent. 

It  is  an  interesting  fact  that  in  those  cases  in  which  the  urine  was  used 
both  before  and  after  delivery,  no  essential  difference  was  noted,  for  the 
reasons  that  in  one  case  all  of  the  mice  recovered,  and  in  the  other  two  mice 
died  from  causes  not  referable  to  poisonous  action,  the  two  to  which  refer- 
ence has  already  been  made.  Twenty-seven  of  these  mice  were  used  for  ex- 
])erimental  purposes  for  the  first  time,  and  twenty-one  had  been  used  before. 
Of  the  former,  twenty-four  recovered  and  three  died;  of  the  latter,  sixteen 
recovered  and  five  died.  Two  of  the  fresh  mice  should  not  be  included  for 
reasons  already  stated,  a  fact  which  makes  the  mortality  in  fresh  mice  one 
in  twenty-five,  or  4  ])cr  cent.,  while  that  of  mice  which  were  used  more  than 
once  was  five  in  twenty-one.  or  nearly  24  per  cent.  This  fact  would  seem 
to  be  conclusi\e  that  repeated  injections  did  not  produce  immunity,  did  not 
lessen  the  sUscejitibility. 

CULTURES 

The  following  table  shows  the  number  of  cultures  made,  the  day  upon 
which  they  were  made,  kind  of  urine  used,  and  whether  the  culture  w-as 
made  upon  gelatin  or  agar-agar.' 

IIKST   i>.\v 

C.cdatin  .\gar-.\gar 

Unboiled    6  3 

LSoiled    6  3 

SlX'ONl)  D.W 

Unboiled    4  3 

Dniled   4  3 

Unboiled    4  3 

Boiled   5  3 

These  cultures  were  examined  in  twenty-four  and  forty-eight  hours. 
The  presence  or  absence  of  growths  is  shown  in  the  follc\\  ing  tables: 


(ledatin 

.\gar-Agar 

6 

0 

6 

2 

L-nboilc<l    

Boiled   

■  .\ttenlion  is  n-caHc(l  to  the  fatt  that  these  cultures  were  niaile  at  the  time  of  making  the 
injections;  that  is,  the  tirst  day  represented  the  time  from  three  to  twelve  hours  after  drawing 
the  urine,  the  second  day  from  twenty-seven  to  thirty-six  hours,  and  the  fourth  day  from  seventy- 
live   to  eighty-four   hours. 


ROBERT  ir.  STILIVART 


SECOND  DAY 

Gedatin       Agar-Agar 

L'nlmilcd    4  2 

Boiled    4  3 

I'orKTu  ^A^• 

Unboiled    4  1 

Boiled  5  2 

C.NdWTUS  IX  TWF'N'I'V-rdl'R    HIll-KS 
riKST    DAV 

Unboiled    : 0  3 

Boiled   0  1 

SECOND  DAY 

Unboiled    0  0 

Boiled   0  0 


Unboiled    0  2 

Boiled   0  1 

NO    CKOVVTJIS    IX    E(iNT\-i;iGllT    JIOUKS 
riKST    DAY 

Unboiled    4  0 

Boiled   5  1 

SECOND  DAY 

Unboiled    4  2 

Boiled   4  3 

Fourth  day 

Unboiled    3  1 

Boiled  4  2 

c.KowTiis  IX  FOK'r\-i-:i(;iiT  hours 

FIRST    day 

Unboiled    2  3 

Boiled   1  1 

SECOND  DAY 

Unboiled    1  Q 

Boiled   0  0 

Fourth  day 

Unboiled    1  2 

Boiled   1  1 

Page 


RAKSOHOFF  MEMORIAL  VOLUME 


It  will  be  seen  that  of  the  twenty-nine  cultures  which  were  made  upon 
gelatin,  all  were  sterile  in  twenty-four  hours,  and  twenty-four  showed  no 
growths  even  in  forty-eight  hours,  while  of  the  eighteen  cultures  made  upon 
agar-agar,  ten  were  sterile  in  twenty-four  hours,  and  nine  showed  no  growths 
in  forty-eight  hours.  Whether  this  greater  disposition  on  the  part  of  the- 
latter  substance  to  develop  colonics  was  due  to  faulty  preparation  or  to  its 
being  a  better  culture  medium,  can  not  be  determined  by  anything  in  this 
work.  The  probabilities  are  that  there  was  less  care  exercised  in  drawing 
the  urine  which  was  used  in  these  series  than  in  the  gelatin  series,  because 
of  the  six  deaths  which  were  fairly  attributable  to  poison  in  the  urine,  four 
occurred  in  the  agar-agar  series.  This  receives  some  confirmation  from  the 
fact  that  in  the  agar-agar  series,  boiled  and  unboiled  urine  showed  a  nearly 
equal  proclivity  to  the  development  of  colonies,  whereas  in  that  series  in 
which  gelatin  was  used  unboiled  urine  showed  a  much  greater  tendency  to 
the  development  of  colonies  than  did  the  boiled  urine. 

No  difference  in  the  development  of  colonies  could  be  discovered  be- 
tween the  urine  taken  ante-partum  and  that  taken  post-partum,  but  not  much 
stress  can  be  laid  on  this  fact,  as  there  were  but  two  patients  whose  urine 
was  so  taken. 

C.\USE  OF   DE.^TH 

A  careful  post-mortem  examination,  which  included  the  blood,  was  made 
upon  each  mouse.  The  following  table  shows  number  of  case,  amount  of 
urine  injected,  cause  of  death,  whether  urine  was  unboiled  or  boiled,  from 
which  day  urine  was  taken,  sterility  or  infection  of  urine  at  time  of  death, 
and  time  in  which  death  occurred : 


1  i  IS  minims     Inanition 

2  i  24  minims  I   Septicemia 

3  120  minims  '   Injury  (?) 


4  \  25  minims  '  Sept 

5  !  25  minims     Septicemia 

6  20  minims     Septicemia 
i  I  .        . 

7  !  25  minims  t   Septicemia 

8  20  minims'  Septicemia 


Bnik-a 

Unboiled 
Boiled 

Unboiled 
Unboiled 


First    Day 
Fourth  I)a\ 
iFirst   Dav 

1 

IFirst   Uav 

ISecond  I)a\ 


Sterile. 
Sterile. 
Sterile. 


15  days 
,?5  hour> 
10  min. 


hours 


Unboiled    ISecond  Day 

Unboiled   IFourth  Dav 

1 


.\uiiierous  colonies 
Sterile  24  hours;  nume 

ous  colonies  3rd  day    12  hours 
"Loaded"  in  24  hours.     '12  hours 

1 
Loaded  in  48  hours.         18  hours 
Loaded  in  24  hours         '24  hours 


The  first  three  specimens  were  from  the  same  patient.  Nos.  1  and  2 
was  taken  nine  days  before  delivery,  and  Xn.  ,^  twelve  hours  after  de- 
livery. 

The  next  three  specimen>  were  all  taken  about  six  weeks  before  delivery 
from  the  same  patient.  Two  control  experiments  were  made  from  urine 
laken  from  the  saine  patient  at  the  same  time,  but  which  was  not  used  until 
the  fourth  day.  Both  mice  recovered,  although  the  unboiled  urine  showed 
two  hundred  (  ?)  colonies  and  the  boiled  urine  was  sterile. 

The  last  two  specimens  were  taken  from  same  patient  less  tlian  four 
weeks  before  delivery. 


ROBERT  W.  STEWART 


In  not  one  of  these  mice  was  there  any  macroscopic  evidence  of  peri- 
tonitis or  injury  to  the  abdominal  organs.  In  Nos.  1  and  3  nothing  was 
found  microscopically  in  the  blood.  These  are  the  mice  whose  deaths  were 
attributed  to  inanition  and  injury,  respectively,  as  has  already  been  ex- 
plained. In  No.  2  rather  large  bacilli  were  found  in  the  blood ;  in  No.  4 
small  ovoid  bacilli  were  present ;  in  Nos.  5  and  6  the  bacilli  were  large :  in 
Nos.  7  and  S  diplococci  were  found. 

Unboiled  urine  was  injected  in  all  those  cases  of  death  in  which  septi- 
cemia was  diagnosed,  or  in  which  micro-organisms  were  found  in  the  blood, 
and  it,  therefore,  is  a  fact  of  considerable  significance  that  the  boiled  urine, 
which  was  drawn  at  the  same  time  as  the  unboiled,  and  which  was  injected 
at  the  same  time,  did  not  kill  in  a  single  instance. 

As  far  as  could  be  ascertained  none  of  these  mice  had  convulsions  before 
death.  This  is  largely  surmise,  however,  because  in  most  cases  the  animals 
were  found  dead.  In  the  few  cases  in  which  the  death  struggle  was  observed 
no  convulsions  occurred. 

If  all  this  work  be  taken  in  review  it  will  be  seen  that  urine  collected — 
that  is,  passed  by  patient  over  boric  acid — evidently  contains  a  convulsive 
poison  which  is  deadly  in  100  per  cent,  of  the  cases,  to  rabbits  and  white 
mice,  whether  the  urine  be  concentrated  or  unconcentrated ;  that  when  the 
urine  is  drawn  by  catheter  under  strict  surgical  asepsis,  the  mortality  is 
greatly  reduced,  and  that  when  the  urine  is  so  drawn  and  immediately  boiled 
the  mortality  is  practically  nothing.  This  contrast  at  once  suggests  the  pos- 
sibility of  error  in  the  deductions  which  have  been  drawn  by  investigators 
who  have  used  the  boric  acid  method,  a  method  which  has  undoubtedly 
been  followed  when  the  urine  is  sent  from  any  distance,  or  has  been  allowed 
to  stand  two,  three  or  four  days  before  use  for  experimental  purposes. 

Even  in  the  writer's  work  asepsis  plays  the  important  role,  because  in 
the  early  ])art  of  1899  the  manipulations  were  made  practically  under  his 
supervision,  and  the  mortality  was  reduced  to  16  per  cent.,  while  in  the 
latter  part  of  the  same  year  the  drawing  of  the  urine  was  not  done  by  his 
own  assistants,  consequently  could  not  be  so  carefully  supervised,  and  the 
mortality  rose  to  much  greater  proportions.  The  experiments  of  1900  were 
again  under  his  direct  care  and  the  mortality  fell  again  to  the  figures  of  the 
early  part  of  1899.     Forchheimer's  individual  work  confirms  this  statement. 

The  relation  of  mortality  to  sterility  or  infection  of  the  urine  at  the  timr 
of  the  death  of  the  animal  is  very  interesting. 

The  table  shows  that  two  specimens  of  boiled  urine  which  were  sterile 
at  time  of  injection  and  remained  sterile  afterwards,  killed  mice — the  two 
which  have  been  excepted  throughout  these  tables ;  two  specimens  of  fresh 
urine  showed  no  growths  in  twenty-four  hours,  but  developed  numerous 
colonies  in  the  succeedings  days;  three  specimens  of  fresh  urine  were  con- 
taminated within  twenty-four  hours,  and  one  in  forty-eight  hours.  In  other 
words,  all  of  the  fresh  urine  which  killed  mice  must  have  contained  micro- 


RAXSOHOFF  MEM0KL4L  VOLUME 


organisms  at  the  time  of  the  injection,  and  in  every  case  septicemia  or  the 
presence  of  bacilH  could  be  demonstrated  in  the  blood.  It  is  reasonable  to 
suppose  that  these  organisms  either  existed  in  the  blood  of  the  mothers,  in 
their  laladders,  or  were  introduced  into  the  urine  during  the  manipulations. 
The  women  were  all  healthy,  had  no  fever,  nor  other  systemic  disturbances, 
no  anorexia  nor  local  deviation  from  the  normal,  and  consequently  could 
not  have  had  blood  so  saturated  with  bacilli  as  to  infect  the  urine.  The  ab- 
sence of  epithelium,  albumin,  blood  and  pus  cells  and  the  freedom  from  pain 
on  urination,  prove  there  was  no  cystitis.  As  the  source  of  the  contamination 
there  is  left,  then,  only  the  manipulations.  This  position  is  strengthened 
by  the  fact  that  the  septicemia  could  not  have  been  due  to  the  presence  in 
the  blood  of  these  animals  of  bacilli  which  only  became  virulent  because 
of  the  injection,  for  the  simple  reason  that  numerous  other  animals  had 
been  kept  in  the  cages  with  the  ones  which  died,  had  gone  through  the  same 
process  of  experimentation  and  yet  recovered.  Therefore,  it  seems  to  the 
writer  that  any  other  view  of  the  cause  of  death  than  infection  of  the  urine 
at  the  time  of  catheterization  or  during  some  of  the  subsequent  manipula- 
tions would  be  illogical  and  strained. 

Not  that  the  writer  means  to  imply  that  imperfect  oxygenation  of  food 
or  tissue  metamorphosis,  with  consequent  production  of  uric  acid,  carbonic 
acid,  paraxanthin  and  the  xanthin  bodies  generally,  may  not  mean  the 
poisoning  of  the  system,  as  has  been  claimed  by  so  many  distinguished 
authorities.  Nor  is  he  willing  to  say  that  these  substances  are  not  thrown 
out  of  the  system  by  the  kidneys.  Above  all,  he  does  not  wish  to  be  under- 
stood as  claiming  that  bacteria  are  the  sole  cause  of  death  in  the  animals 
which  have  been  used  by  other  experimenters. 

At  the  same  time  one  can  not  deny  that,  as  far  as  the  present  work 
goes,  there  is  good  reason  for  believing  that  what  has  heretofore  been 
attributed  to  poisons  generated  in  the  human  body  was  often  due  to  micro- 
organisms which  must  have  been  introduced  into  the  urine  after  it  was 
voided.  The  one  claim  which  Forchheimer  and  the  writer  do  make  is 
that  the  methods,  and  consequently  the  deductions  of  other  experimenters, 
are  open  to  serious  objection,  and  that  the  intra-abdominal  injection  of 
urine  which  has  been  drawn  by  catheter  under  strict  asepsis  is  freer  from 
objection  than  the  intravenous  method. 

Finally,  while  the  writer  is  diffident  in  claiming  too  much  for  the  elifect 
which  bacteria  may  produce  in  this  line  of  work,  it  is  a  significant  fact 
that  in  his  own  cases  75  per  cent,  of  the  deaths  can  not  be  attributed  to 
any  other  cause  than  bacteria. 

Note — Dr.  .\llan  Ramsey  did  the  bacteriological  part  of  this  work  and 
materially  assisted  in  all  of  it.    He  deserves  the  credit  and  has  my  gratitude. 

LITER.-VTl'RE. 

1.  Volhard:    M.  .   ,1   .  h,      f     (,,li     u.    Gyn.,   Bd.    V.   1S9T. 

2.  Ludwig.    IK    ^.1      .       \1    ,,,!,, In.    f.    Gcb.    u.    Gyn.,    Bd.    I,    1S05. 
■      3.     Tarnier  el   (  li.unl, ,  l>  n.  :    >,.,•.  d.Biol.,  1SU2,  No.   U. 

4.  Bouchard:    "".Vulu    liiluxi^,ilu.ii." 

5.  Stewart:  Amer. 
0.     Stewart;  Amer. 

Page  5j8 


T?1E  EARLY  DIAGNOSIS  OF  SYPHILIS  AXD  A  COMPARATIVE 
STANDARDIZATION   OF  THE  TREATMENT.* 

E.  r,.  Tauiuck,  ^r.D., 

Cincinnati. 

In  the  problem  of  syphilis  it  is  im])erative  to  secure  an  earlier  and  more 
efficient  diagnosis  of  the  disease  than  is  the  case  at  the  present  and  a 
more  generalized  effective  treatment.  'J'his  should  lie  the  keynote  of  our 
endeavors. 

The  early  diagnosis  of  .syphilis  is  an  unknown  quantity  to  many  men 
who  are  practicing  medicine  in  our  times.  To  men  who  have  the  older 
ideas  of  the  disease  to  guide  them,  ideas  that  are  firmly  planted  in  their 
minds  by  a  couple  of  decades  of  practice,  it  seems  almost  sacrilege  to  insist 
that  waiting  for  secondaries  is  a  criminal  action  and  that  we  lose  the  benefit 
of  the  one  psychologic  moment  in  the  life  history  of  syphilis  when  we  can 
seize  our  real  opportunity. 

The  definite  diagnosis  in  the  early  primary  stage  before  the  spirochete 
has  spread  to  the  lymphatic  system  near  the  primary  lesion  and  before  the 
serologic  reaction  is  positive  is  the  one  and  only  time  that,  taken  advantage 
of,  may  lead  to  success,  and  it  is  the  time  for  action  instant  and  effective. 
This  is  the  time  for  radical  cure  if  such  is  possible.  An  injection  of  ars- 
phenamin  here  can  put  an  immediate  end  to  infectivity  of  the  case.  A 
sterilization  complete  and  entire  seems  possible  here.  The  suppression  of 
the  biologic  and  serologic  evidence  of  the  disease  is  possible  and  may  be 
probable  here.  This  should  lie  our  treatment  for  paresis,  tabes  dorsalis, 
iritis,  etc. 

PROPHYLAXIS  OR  TRF.ATMRXT  THAT  WILL  PRE\'EXT  THESE  COXIDI- 
TIOXS 

The  first  week  or  so  of  the  initial  lesion,  while  syphilis  is  still  a  local 
condition,  is  the  time  that  we  should  emiiloy  every  energy  and  endeavor 
of  our  diagnostic  and  therapeutic  armamentarium  to  cure,  for  never  again 
in  the  picture  of  syphilis  for  the  individual  patient  or  the  state  will  this 
moment  return. 

Our  public  health  services,  medical  colleges,  hospitals  and  clinics  must 
teach  this  point  and  ever  impress  it  on  all  in  contact  with  them ;  that  is, 
the  student  groups,  the  nursing  groups  and  the  public  in  general,  these 
facts  and  necessities. 

The  dark  field  examination  must  he  a  routine  at  the  clinics,  in  the  hos- 
pitals and  in  our  private  practice.  The  organism  must  be  known  and 
recognized  by  all. 


nbei-   29,    1919. 


KAXSOHOFF  MEMORIAL  VOLUME 


The  newer  staining  methods,  such  as  the  MedaHa  method,  must  be 
taught  generally.  There  can  be  no  valid  objection  to  teaching  the  profes- 
sion of  the  future  and  the  present  the  only  means  of  diagnosis  for  the 
period  when  the  dangerous  sequehe  may  be  mastered  and  dominated  by  us. 

Every  sore,  whether  on  the  genitalia  or  elsewhere,  is  or  should  be  open 
to  a  suspicion  of  chancre  and  should  be  repeatedly  examined  for  Spiro- 
cliacta  pallida.  Every  papule,  nodule,  crack,  excoriation  and  herpetic  or 
other  erosion  should  be  viewed  with  the  possibility  of  an  initial  lesion  and 
should  be  examined  for  Spirochacta  pallida.  Chancroids  should  not  be 
accepted  as  uncomplicated  with  syphilis;  double  infection  is  always  pos- 
sible. 

.\ntiseptics  applied,  especially  mercurial^.,  make  tin-  finding  of  Spiro- 
chacta pallida  diflicult  or  almost  impossible,  and  because  of  this  we  should 
teach  that  no  mercurial  dressings,  or  better  still,  no  antiseptics,  should  be 
applied  to  any  lesions  until  the  examination  for  Spirochaeta  pallida  has 
been  made,  and  if  any  have  been  used,  it  should  be  made  a  routine  to  irri- 
gate thoroughly  with  physiologic  sodium  chlorid  solution  and  to  apply  a 
wet  dressing  of  the  solution  for  twelve  hours  or  more  before  examining 
for  Spirochacta  pallida.  To  obtain  Spirochacta  pallida,  a  definite  method 
is  important.    We  have  used  in  the  Cincinnati  General  Hospital  this  method: 

The  surface  of  the  lesion  is  wiped  with  a  cotton  sponge  to  remove 
superficial  organisms.  The  wound  may  be  rubbed  or  teased  lightly,  but 
one  should  not  cause  bleeding;  just  an  oozing  that  will  give  serum  to  trans- 
fer to  a  new  clean  side  and  slip  should  be  produced.  Immersion  oil  is  put 
on  both  the  under  surface  of  the  slide  and  upper  surface  of  the  cover.  This 
will  give  a  continuous  airless  medium  from  dark  field  to  objective.  A  focus 
with  fine  adjustment  should  be  secured  until  one  gets  a  dark  background 
with  the  glistening  moving  particles  in  white  rings.  Then  a  search  for  the 
twisting  spirochetes  may  be  instituted. 

^\s  a  professional  body,  let  us  be  honest  and  acknowledge  that  we  have 
not  spread  the  vital  importance  of  early  diagnosis.  It  has  taken  a  world 
war  to  impress  on  us  that  the  modern  conceptions  of  syphilis  have  not 
been  taught  in  our  medical  colleges.  We  have  zealously  striven  to  white- 
wash the  episodes  occurring  in  the  wrecks  due  to  this  disease.  We  have 
had  clinical  characteristics  and  endless  discussions  as  to  secondaries  and 
tertiaries  and  neurosyphilis,  forgetting  that  we  were  proving  our  guilt  in 
this  very  manner,  and  now  we  must  scrap  our  clinical  dififerences  and  turn 
to  laboratory  diagnosis  to  the  finding  of  Spirochacta  pallida.  I  do  not 
mean  here  the  serologic  diagnosis,  for  then  we  are  losing  our  great  oppor- 


TR.MXIXG   THE    PROFESSION    TO    E.\RLV    DI.\C-XOSIS 

How  can  we  create  this?    This  is  our  tremendous  duty.     You  must  all 
aid  this.     We  must   aid  all  the  men   who   will  do  dark-field  work   in  the 


E.  B.  TAUBER 


smaller  towns  and  villages  and  show  them  and  others  by  our  support  that 
Ave  are  back  of  them.  The  internists,  the  surgeons  of  the  smaller  localitic- 
must  call  on  the  man  in  that  locality  who  has  special  knowledge  of  syphilis, 
and  this  will  cause  the  demand  to  be  supplied.  We  must  send  to  Coventr\ 
the  man  who  cauterizes  or  applies  some  medicament  to  the  sore  on  the 
penis  or  other  location  before  advice,  and  competent  advice  at  that,  is  given 
and  the  dark-field  tests  are  made. 

In  early  .syphilis,  systematic  treatment  must  be  immediate  and  nui.^t  be 
pushed  vigorously ;  sledge-hammer  treatment  here  is  indicated,  not  feather- 
duster  types  of  treatment.  vSyphilogra]:ihers  will  doubtless  agree  that  the 
efifective  time  for  arsplienamin  is  early,  before  the  serologic  tests  are  posi- 
tive. So,  then,  this  places  on  us  the  burden  of  outlining  a  method  or 
scheme  for  treatment  that  shall  be  more  or  less  standardized.  Here  I  mean 
a  treatment  for  the  majority  of  cases,  not  for  individual  ones;  also  a  treat- 
ment that  will  not  be  inflexible  but  one  that  has  been  tried-  over  a  long 
period  of  time  in  a  sufficient  number  of  cases  to  at  least  have  the  merit  of 
being  successful.  The  outline  I  wish  to  submit  has  been  tried  at  the  Cin- 
cinnati General  Hospital,  the  outpatient  dispensary,  the  night  venereal 
clinic  and  in  my  private  practice,  all  of  which  I  have  under  my  control, 
and  our  results  have  been  very  good.     Our  method  is  as  follows : 

A  SUCCESSFUL  METHOD  OF  TREATMENT 
Courses  of  from  four  to  six  intravenous  injections  of  arsphenamin  of 
from  0.3  to  0.6  gm.  at  intervals  of  from  three  to  seven  days  are  given,  com- 
bined with  mercury.  Here  we  may  with  one  or  two  such  courses  eft'ect  a 
cure.  But  even  with  such  vigorous  treatment  a  second  or  third  course  of 
arsphenamin  of  the  same  type  is  advisable  after  a  two  months'  interval, 
given  with  the  same  courses  of  mercury. 

In  all  cases,  after  the  Wassermann  test  is  positive,  I  believe  at  least 
three  such  courses  of  l/ofh  arsphenamin  and  mercury  to  be  the  minimum, 
and  more  can  be  given  as  indicated.  I  believe  that  mercury,  given  either 
by  intramuscular  injection.s  ol  solulile  or  insoluble  preparations  or  by  rubs, 
is  of  great  aid  to  our  arsphenamin  therapy,  and  in  the  rational  cure  of 
syphilis,  mercury  and  arsphenamin  must  be  combined. 

The  courses  of  mercury  should  be  from  ten  to  twelve  injections,  at 
weekly  intervals,  of  an  insoluble;  or  from  twenty-four  to  tliirtv,  given 
every  other  day,  of  a  soluble,  or  thirty  to  forty  daily  inunctions.  T  nivseh 
believe  in  giving  one  course  of  each  type  of  mercury  with  each  course  of 
arsphenamin.  Serologic  tests  should  be  made  once  a  month  at  first,  and 
later  at  two  month  intervals,  until  the  test  seems  to  become  permanently 
negative  as  shown  Ijy  at  least  five  unbroken  negative  tests,  each  six  months 
apart,  with  no  treatment  and  no  clinical  evidence  of  syphilis  before  we 
should  become  in  the  least  optimistic  in  regard  to  the  case  as  being  checked 
or  cured. 


RAASOHOFF  MEMORIAL  VOLUME 


It  is  my  opinion  that  provocative  injections  and  spinal  puncture  with 
the  colloidal  gold  test  may  be  made;  but  there  is  a  difference  of  opinion 
as  to  this  need,  except  in  cases  that  require  these  special  methods. 

Tn  late  syphilis,  mercury  and  iodids  should  he  ])Ushed  in  courses  with 
arsphenaniin  given  in  the  same  way. 

In  secondary  syphilis,  the  first  year,  three  courses  as  above  outlined  of 
from  six  to  eight  doses  of  arsphenaniin  in  each  course,  combined  with 
mercury,  and  not  less  than  three  of  such  courses  are  indicated. 

The  second  year,  if  the  Wassermann  test  remains  positive  or  there  is 
recurrence  of  any  lesion,  practically  a  repetition  of  the  first  year's  treat- 
ment, as  outlined,  will  be  necessary. 

If  the  \\'asserniann  test  is  negati\e  and  remains  negative  and  there  is 
no  recurrence  of  lesions,  at  least  four  doses  of  arsj^henaniin  in  conjunc- 
tion with  two  courses  of  mercury  arc   recommended. 

The  third  year,  if  the  \\'assermann  test  remains  negative  and  there 
have  been  no  recurrences  from  the  first  year,  a  patient  should  pass  into  a 
period  of  observation  with  regular  periods  for  a  serologic  examination. 
If  there  is  any  nerve  involvement  or  tabes  and  paresis,  the  treatment  will 
depend  on  the  individual  case  and  will  be  cavered  by  any  general  methods ; 
but  treatment  must  be  pushed  for  years. 

Congenital  or  hereditary  syphilis  requires  longer  and  more  persistent 
treatment ;  but  again  more  individual  treatment  is  necessary  and  cannot 
be  outlined  in  the  same  way  that  early  acquired  syphilis  can  be.  To  re- 
capitulate, my  outline  is  as  follows  as  regards  standardization  for  early 
.syphilis : 

Arsphenaniin  and  mercury  to  be  given  combined. 

Arsphenaniin.  each  course  from  four  to  six  doses  of  from  0.,i  to  0.6 
gm.  intravenously  at  three  to  seven  day  intervals. 

Mercury  (insoluble),  gray  oil,  mercuric  salicylate,  twelve  doses  at 
weekly  intervals,  dose  from  three  to  five  minims. 

Mercury  (soluble),  twenty-four  to  thirty  injections  of  mercuric  cyanid 
or  mercuric  chlorid,  given  every  other  day. 

Rubs,  twenty-four  to  thirty  given  every  day. 

First  Year. — First  course  of  treatment,  from  two  to  two  and  one-half 
months.  Rest,  one  month.  Second  course  of  treatment,  from  two  to  two 
and  one-half  months.  Rest,  two  months.  Third  course,  from  two  to  two 
and  one-half  months. 

Second  Year. — If  Wassermann  is  negative,  rest  after  tiiird  course  for 
four  months;  mercury,  two  months;  rest,  four  months;  mercury,  two 
months. 

If  Was.sermann  is  positive,  rest,  two  months;  course  of  arsphenaniin 
and  mercury,  two  months;  rest,  two  months;  arsphenaniin  and  mercury, 
two  months;  rest,  two  months;  arsphenaniin  and  mercury,  two  months: 


E.  B.  TAUBER 


Third  Year. — If  W'assermann  is  negative,  patient  passes  to  period  of 
oljservation  with  regular  serologic  examinations. 

If  W'asserniann  is  positive,  rest  after  last  course,  two  months;  arsphena- 
niin  and  mercur}-,  two  months;  rest,  two  months;  mercury  course,  two 
months;  rest,  two  months;  ars])lienamin  and  mercury,  two  months,  and  so 
on,  heing  controlled  hy  serologic  findings. 

It  is  not  easy  to  state  when  a  cure  is  accomplished;  hut,  in  general,  we 
can  only  say,  by  intensive  therapy  safety  can  be  secured  and  in  most  cases 
a  cure  can  be  effected.  This  may  result  in  overtreating  in  some  cases,  but 
it  is  better  to  err  in  this  way  than  to  undertreat  a  single  one,  and  some 
cures  require  a  definite  amount  of  treatment  on  a  definite  basis,  if  the 
needed  results  are  to  be  obtained.  Therefore,  before  patients  are  told 
they  are  well,  even  after  repeated  negative  Wassermann  tests  without 
treatment  { for  negative  Wassermann  tests  during  treatment  only  indicate 
that  progress  is  being  made),  I  consider  it  necessary  that  at  least  two  or 
three  years  of  negative  serologic  tests  w-ithout  treatment  or  recurrence  of 
any  symptoms  indicative  of  syphilis  shall  elapse  before  we  can  even  say 
that  we  think  the  pathologic  condition  is  eliminated.  In  so  brief  a  paper 
I  could  cover  only  majority  cases,  and  no  attempt  has  been  made  as  re- 
gards treatment  or  outline  for  individual  cases. 

COXCLUSIOXS 

1.  Xo  single  sign  of  improvement  should  be  accepted  as  definite  or 
fmal,  and  treatment  should  not  he  stopped  at  such  indication.  Only  cessa- 
tion of  all  around  symptoms  is  indicative,  and  that  only  if  it  continues 
through  years. 

2.  Arsphenamin  therapy  is  necessary,  since  it  controls  infecti\ity  and 
contagion.     It  yields  quick  results. 

3.  Mercury  is  essential  but  as  a  splint  to  our  arsenic  therapy  and  as  an 
aid  to  permanence  in  cure. 

4.  Most  syphilis  is  undertreated.  Sledge-hammer  blows  are  indicated. 
Overtreatment  is  to  be  preferred  to  undertreatment. 

5.  It  is  better  to  be  overconservative  rather  than  optimistic  in  staling 
that  a  cure  has  been  effected.  Our  modern  therapy  is  still  in  too  infantile 
a  stage  to  justify  anything  but  overconservatism. 

I  believe  that  specializing  and  efficiency  tendencies  can  be  obtained,  and 
very  ably,  in  the  treatment  of  syphilis. 

Hospitals  and  clinical  centers  in  our  larger  cities  can  be  used  by  smaller 
centers.  The  extension  of  war-time  methods  in  the  army  to  civil  practice 
will  and  should  come. 

In  a  few  words,  I  bclie\-e  syphilis  is  as  easily  prex'entable  as  other  in- 
fectious diseases.    With  syphilis  an  actual  condition,  it  must  be  recognized 


RAXSOHOFl-  MEMORIAL  VOLUME 


early  and  treated  early  if  its  economic  results  are  to  be  prevented.  Thu-^ 
our  problem  is  early  recognition  and  early  treatment.  The  early  period 
is  its  period  of  greatest  transmission  ;  al>o  the  period  in  which  our  chances 
of  curing  a  patient  are  greatest.  This  places  the  burden  squarely  where 
it  belongs,  on  us,  the  medical  profession,  and  also  on  the  public  health 
service,  medical  schools,  hospitals  and  clinics.  These  different  agencies 
must  individually  disseminate  knowledge,  acquire  competent  teachers,  and 
adequate  equipment  to  give  adequate  treatment  and  to  graduate  competent 
physicians.  This  means  that  syphilis  needs  centralization,  efficiency,  con- 
trol, and  the  teaching  of  the  early  diagnosis  of  syphilis  and  a  comparative 
standardization  of  its  treatment. 


INHALATION  EXPERIMENTS  ON  INFLUENZA  AND  PNEUMO- 
NIA, AND  ON  THE  IMPORTANCE  OF  SPRAY-BORNE 
P-ACTERTA  IN  RESPIRATORY  INFECTIONS.* 

WiLLiAjr  B.  Wherry  and  C.  T.  Buttf.rfifxd. 
Cincinnati. 

While  the  influenza  viru.s  appeared  to  be  of  reduced  virulence  during  the 
outbreak  of  February  and  March,  1920,  the  occasional  occurrence  of  a 
family  outbreak,  or  of  rapid  death  due  to  pulmonary  edema,  seemed  to  in- 
dicate that  it  was  identical  with  that  present  in  the  outbreak  of  1919.  We 
feel  particularly  sure  that  we  were  dealing  with  cases  of  influenza  in-  the 
family  of  S.,  because  the  mother,  father  and  eight  children  all  came  into 
the  hospital  at  once.  Most  of  these  ten  patients  had  bronchopneumonia 
and  one  purulent  pleuritis.  Cases  R.  and  S.,  B.  and  B.  and  T.  were  of  a 
milder  type,  although  B.  and  T.  had  secondary  bronchopneumonia.  These 
cases  were  chosen  because  most  of  them  had  been  ill  for  only  a  day  or 
two  at  the  time  the  material  was  collected. 

Thirty-eight  cases,  including  those  just  cited,  were  examined  bacterio- 
logically.  All  aerobic,  partial  tension  and  anaerobic  blood  cultures  were 
negative.  For  the  throat  and  sputum  cultures  we  used  +  0.5  agar  con- 
taining 5  per  cent,  of  rabbit  blood.  Incubation  was  at  37  C.  under  aerobic, 
partial  tension  and  anaerobic  conditions.  B.  influenzae  was  isolated  from 
twelve  cases.  Six  of  the  twelve  were  from  the  family  S..  who  all  became 
ill  at  once.  From  the  father  of  this  family  we  failed  to  isolate  B.  in- 
fluenzae, and  he  was  ill  for  months  with  streptococcus  empyema.  In  six 
cases  B.  influenzae  was  the  predominating  organism  and  in  four  it  was 
present  in  pure  culture. 

When  B.  influenzae  was  grown  at  partial  tension  it  retained  its  minute 
bipolar  form  and  showed  less  tendency  to  involution  than  when  grown 
aerobically.  All  the  strains  were  strictly  hemoglobinophilic  while  the 
Koch-Weeks  bacillus  was  isolated  on  aerobic,  partial  tension  and  anaerobic 
slants  of  ascites  agar,  and  could  be  subcultured  on  this  medium.  All  strains 
failed  to  produce  indol  in  hemoglobin  broth  when  the  sulphuric  acid-sodium 
nitrate  test  was  applied.  However,  the  growth  in  our  broth  was  scanty. 
Most  of  the  associated  bacteria  belonged  to  the  pneumococcus,  hemolytic 
streptococus  and  staphylococcus  groups.  No  colonies  that  might  have 
represented  the  B.  enteritidis  (type  M  5),  which  appeared  in  the  sprayed 
animals,  were  noted,  and  it  is  not  likely  that  they  were  overlooked,  for  M  r> 
colonies  on  blood-agar  plates  at  partial  tension  are  a  \ivid  green — as  are 
those  of  typhoid,  paratyphoid  D.  and  B.  enteritidis. 


RAXSOHOFF  MFMORIAL  J-()LUMH 


Antigens  from  all  strains  tested  were  prepared  at  one  time  and  kept  under  the 
same  conditions.  Cultures  were  washed  and  suspended  in  0.9%  salt  solution,  killed 
at  65  C.  for  thirty  minutes,  freed  of  clumps  and  preserved  with  0.5%  phenol. 

-Agglutinating  serum  for  B.  influenzae  and  the  Koch-Weeks  bacillus  were  pre- 
pared by  inoculating  rabbits  with  living  cultures.  In  the  case  of  M  5  a  dead  anti.gen 
was  necessary.  The  scrums  had  a  rather  low  titer,  about   1  :800. 


T.\P.I, 


ACCLUTIN 

ATIOS     AND    AbSORPTIHX     REACTI 

INS 

Mother  .Antiserum 

Koch  Weeks  Antiserum 

Designation    of    Strains 

Simple 

Homnlugous 

Simple 

HomoloKOus 

.XgRlutination 

Absorbed 

Agglutination 

Absorbed 

1.     MollKr 

1 
-f-              1              + 

2.     R 

-r              1              -f- 

-1-              1               P 

+ 

P 

+              I              + 

5.     M 
(..     S 

+              1              -1- 

— 

+              1                P 

__ 

8.      \ 

__ 

9.      Sum 

10.      K 

—              1 

11.     Uo 

—              1 

12.      Koch  Weeks 

-t- 

+ 

As  shown  in  Tal)lc  1,  four  of  the  strahis  from  the  f;iniily  S..  mother, 
1!.,  S.  and  M.,  and  strain  C  from  a  healthy  individual,  are  probahly  iden- 
tical. One  other  of  the  family  strains,  H.,  is  somewhat  related  to  this 
group,  but  is  about  as  closely  related  to  the  Koch-Weeks  bacillus.  This 
agrees  with  the  work  of  others  in  showing  that  there  are  distinct  serologic 
groups  among  the  influenza  bacilli  and  that  some  strains  are  closely  related 
to  the  Koch-Weeks  bacillus. 

Blood  serum  from  some  of  the  recovered  members  of  family  S.,  who 
had  harbored  B.  influenzae,  contained  no  agglutinins  for  this  organism. 


yXTTEMPTS   TO   TR.WSMIT    IXFLUl'.XZA   TO   WHITE    MICE   A\D   RATS, 
GUINEA  PIGS  AXn  RAlUilTS  V.Y  .\1EA.\S  OF  SPRAYED  SPUTUM 

Sputum,  or,  when  this  could  not  be  obtained,  material  swabbed  from 
the  tonsillar  area,  but  generally  both,  were  thoroughly  shaken  with  0.9  per 
cent,  salt  solution  and  sprayed  by  means  of  a  \'ilbiss  atomizer  within  half 
an  hour  after  collection.  The  animals  were  ])laced  in  a  metal  box  about 
12  X  10x6  inches,  jirovided  with  a  glass  window  and  air  outlets.  The  spray- 
ing was  continued  until  the  chamber  was  filled  with  vapor.  This  was  re- 
peated at  intervals  tiiitil  15-20  c.c.  had  lieen  sprayed,  .\fter  from  30-60 
minutes  the  animals  were  removed  from  the  cage  and  each  series  kept  in 
separate  cages.  These  were  scalded  with  hot  water  before  they  were  used 
for  any  given  series.  The  sawdust  bedding  was  not  sterilized.  Precautions 
were  taken  to  sterilize  the  drinking  pans  in  the  case  of  all  mouse  experi- 


WILLIAM  B.  WHEKRY  AND  C.  T.  BUTTERFIELD 


ments.  'J'lic  animals  were  fed  on  cracked  maize  and  vegetalile  waste  from 
the  hos]5ital   kitchen. 

It  might  he  noted  here  that  one  of  ns  in  Cincinnati  inoculated  sterile 
milk  with  influenza  sputum  (1919)  audi  incuhatcd  it  at  o7,  24  and  IS  de- 
grees for  fr(jm  1-14  days,  and  fed  it  to  white  rats  and  white  mice.  Of 
ahout  forty  animals  .so  fed  only  two  mice  died,  one  with  pneumococcus 
septicemia,  and  one  with  pneumonia  and  serous  pleuritis  due  to  four  dif- 
ferent hacteria.  None  of  these  hacteria,  singly  or  combined,  produced  in- 
fection when  fed  to  other  mice  in  milk  or  broth,  cultures. 

Table  2  gi\es  the  data  on  these  experiments. 

T.\HLE  2 
Infi,uenz.\-Sputi'm   Spraying  KxpERiMtNT 


|g 

■i 
1 

1, 

x;™ — 

II 

11 

■s 

^1 
.2 

i 

It 

"1 

Us 

h 

c 

5 

-    . 

Spray 

^"S 

,= « 

il  E 

ill 

£-Z 

5 

2/  3/20 

Sputum  S 

5   mice 

4    CI 

i9-;3 

so 

.Ml  like  M5 

killed) 

(MlfM2) 

2/  3/20 

Sputum  S 

Spray 

4  white 

2 

2 
(Wl.^VVJ) 

13 

50 

Sterile 

2/  3/20 

Sputum  S 

Spray 

2  guinea- 

2 

8-80 

ion 

Uke   !\I5 

2/22/20 

^Torsi"- 

Intraperi 
toneal 

pigs 
2  mice 

2 

(f,.-R-3) 

r.-8 

100 

General    infec- 
tion like  M5 

2/23/20 

Mi.\ed  culture 
Ml   plate 

Spray 

2  mice 

2 

(M5.'M(.) 

8-12 

100 

MG  like  M5 

3/  3/20 

^TnM"'- 

Spray 

2  mice 

1 

12 

50 

Like  MS 

2/25/20 

0.,anem... 
Orsan  emul- 

Spray 

2  mice 

0 

0 

0 

2/16/20 

Intraperi- 

2 while 

„ 

0 

0 

sion    Wl.    W2 

toneal 

4/23/20 

ZTcT's 

Spray 

2  mice 

' 

0 

40 

50 

3/23/20 

ZrcT% 

Spray 

2  guinea- 

1 

" 

30 

50 

General    infec- 
tion like  MS 

2/  4/20 

Sputum  cul- 
tures  case    S 

Spray 

6  ''mice 

' 

2 

31-45 

33 

No  growth   ob- 
tained   from 

2/  4/20 

Sputum  cul. 

Spray 

2  «»■-- 

0 

0 

" 

Killed     fnd 
found       nor- 

2/ 4/20 

Sputum  cul- 
tures case   S 

Spray 

2    white 

0 

0 

» 

mal   5/2/20 

2/  4/20 

Sputum  cul- 
tures case   S 

Spray 

1  'rabhit 

1 

I    (Rl) 

8 

ino 

G-l-     coccu. 
present,  lung 
large      num- 

2/ir,/20 

Culture    Rl 

Intravcn- 

2  rabbits 

2 

34-40 

100 

"agent  n.'l  R^ 

intraperi- 

toneal 

3/  2/20 

Sputum 
R   and   S 

Spray 

2  mice 

2 

1 

33-45 

100 

Like  M5 

2/  2/20 

iBj 

Spray 

1   guinea 
PiR 

• 

1 

26 

100 

Like  .M5 

3/  3/20 

Spray 

4 

' 

30-38 

511 

Like    M5.    one 
sterile 

4/  4/20 

Lung  emulsion 
B    and    B    30- 

Intraperi- 
toneal 

2   mice 

' 

' 

50 

Like   M5 

4/  7/20 

LungemuTsLn 

Inlraperi- 

1  mouse 

' 

0 

3 

100 

Like  M5 

3/  5/20 

Sputun,_ 

Spray 

6  mice 

1 

0 

52 

Like    M5    froul 

3/  5/20 

SpuT'.m  -r 

Spray 

6   mice 

2 

0 

72-84 

__!'_ 

Like"M5 

RAXSOHOI-F  MEMORIAL  VOLUME 


Family  S..  Sputum  Spray:  Four  of  five  mice  died  infected  with  a  strain_of  I!, 
cnteritidis"  (type  M5"):  two  of  these  died  of  a  primary  pneumonia  due  to  MS.  By 
the  term  primary  pneumonia  we  mean  pneumonia  without  marked  involvement  of  the 
liver  and  spleen,  which  invariahly  occurs  in  a  general   infection,   i.  r.   after   feeding. 

Of  two  guinea-pigs,  one  died  of  primary  pneumonia  due  to  M  .t.  One  of  two 
mice  and  one  of  two  guinea-pigs  sprayed  with  cxtrcats  of  the  spleen.  li\tr  and  lungs 
of  this  animal  died  of  general  infection  with  M  3. 

Two  of  four  rats  died  of  primary  pneumonia  and  the  long  cultures  yielded  no 
growth,  nor  were  subinoculations  of  organ  extracts  fatal  to  rats. 

Partial  tension  rabbit  blood-agar  plate  cultures,  from  the  sputum  used  for  spray- 
ing the  animals,  were  sprayed  after  twenty-four  hours'  growth  at  37  degrees  Of  six 
mice,  two  guinea-pigs  and  one  rabbit,  only  three  animals  died— two  mice  the  31st  and 
4Sth  day  were  sterile  bacteriologically,  and  one  rabbit  of  primary  pneumonia,  ap- 
parently due  to  a  gram-posiive  coccus,  which,  however,  did  not  appear  in  the  two 
.subinoculated  rabbits. 

R.  and  S.  Sputum  Sfray.—The  two  mice  sprayed  died  of  infection  with  M  5. 
one  of  primary  pneumonia.     The  guinea-pig  died  of  primary  pneumonia  due  to  M  5. 

B.  and  B.' Stutum  of  ^/?.— Of  eight  mice,  four  died,  but  only  one  of  these  had 
pneumonia  due  to  M  5.  Two  had  general  infection  due  to  M  5. 

B.  and  B.  Sfitutn  of  5/5.— Of  six  mice  sprayed  one  died  on  the  52nd  day  of 
general  infection  with  M  5.  The  rest,  which  were  killed  three  months  later,  were 
found  to  be  normal  and  did  not  harlior  M  5. 

Sputum  T. — Of  six  mice  sprayed,  two  died  on  the  72nd  and  84th  days  thereafter: 
one  had  a  general  infection  with  M  S.  The  remaining  four  were  killeil  three  months 
later  and  found  to  be  normal. 

Si<iiiiiiarx. — That  animals  .•>prayed  with  iutluenza  .-putum  coin])ri>e'l 
thirty-three  white  mice,  of  which  four  died  of  primary  pneumonia  and  nine 
of  a  general  infection  with  M  5.  Of  this  same  lot  of  mice,  six  were  sprayed 
with  culture  material  and  of  these  two.  which  died,  were  sterile  on  bacterio- 
logic  examination ;  two  were  killed  and  cultured  two  months  later  and 
found  to  be  uninfected,  and  two  were  used  for  another  experiment  in 
which  they  survied  for  a  month. 

Of  five  guinea-pigs,  two  died  of  primary  pneuinonia;  the  lungs  of  these 
animals  contained  numerous  B.  enteritidis,  which  were  culturally  and  sero- 
logically identical   (agglutination  and  absorption)   with  M  5. 

Of  six  white  rats  similarly  exposed,  two  died  of  a  primary  pneumonia 
tlue  to  an  unrecognized  cau>e  and  not  transmissible  to  rats  by  intraperi- 
loncal  inoculation. 

The  work  of  Krumwiede,  Valentine  and  Kohn'  shows  that  these  animals 
may  develop  spontaneous  infection  with  members  of  the  paratyphoid-en- 
teritidis  group.  We  did  not  encounter  a  single  death  among  our  unused 
stock  due  to  such  bacteria,  nor  were  we  able  to  isolate  such  bacteria  from 
the  intestinal  tract,  liver,  spleen  and  lungs  of  six  normal  inice.  However, 
the  experiments  detailed  in  Table  7  show  that  a  certain  number  of  mice 
which  are  intoxicated  by  killed  cultures  of  M  5  or  by  the  sterile  Berkefeld 
filtrate  of  broth  cultures,  develop  a  secondary  infection  with  M  5.  In  such 
endogenous  infections,  following  intoxication,  pneumonia  occurred  only 
twice  in  forty  animals. 

Furthermore,  of  twenty-nine  mice  si)rayed  with  a  virulent  culture  of 
the  pneumococcus,  only  one  died  of  infection  with  M  5.  and  this  mouse  had 
received  a  previous  dose  of   M  5  toxin.     On  the  other  hand,  as  shown  in 

■Jour.    MkI.    Kcs.,    I'.'iy.    Ml.  \..    W. 


WILLIAM  B.  WHERRY  AND  C.  T.  BUTTERFIELD 


Table  5,  mice  exposed  to  sprayed  cultures  of   M  5  almost  invariably  died 
of  a  primary  pneumonia. 

In  the  light  of  these  data  one  rs  tempted  tu  believe  that  the  animals 
developing  infection  with  M  5  were  injured  in  some  way  by  something  in 
the  influenza  sputum.  Nevertheless,  the  possibility  of  purely  spontaneous 
infection  exists  and  the  question  can  only  be  settled  by  further  work  with 
more  adec^uate  controls,  /.  c.  an  equal  number  of  animals  from  each  lot 
used  for  an  experiment  should  have  l)een  kept  under  identical  conditions  as 
controls. 

IXOCUL.XTIOX  OF  OTHER  .WIMALS 

From  one  of  the  typical  cases,  "R,"  20  c.c.  of  blood  was  obtained.  This  was  used 
to  inoculate  a  series  of  animals  not  generally  used  m  laboratory  experiments  with  the 
hop"  that  a  susceptible  animal  might  be  encountered.  These  were  a  pig,  eight  weeks 
old,  weighing  about  100  pounds,  a  ferret,  an  opossum,  a  salamander,  and  a  black-headed 
nun.     Wone  showed  any  abnormal  symptoms  during  three  months'  observation. 

The  Cultur.m.  .\xd  .V.CLUTix.rrivE  Rel.atioxship  of  M  5  (T.^bles  3  .\nd  4) 

Since  all  the  enteritidis-like  organisms  isolated  from  the  mice  and  guinea-pigs  ex- 
posed to  sputum  sprays  corresponded  in  their  agglutination,  absorption  and  cultural 
characteristics,  we  used  M  5  alone  for  the  comparative  study.  Unfortunately  only  two 
antiserums,  M  5,  with  a  titer  of  1  :800,  and  paratyphoid  B.,  with  a  titer  of  1  ;10,00(), 
were  available.  Table  3  shows  that  M  5  is  entirely  distinct  from  paratyphoid  B.,  but 
that  it  is  indistinguishable  by  this  te.st  alone  from  Danysz  virus  and  from  B.  enter- 
itidis.  However,  the  cultural  results  (table  4)  show  that  Danysz  virus  agrees  with 
paratyphoid  B.  in  its  failure  to  ferment  xylose,  while  M  .i  agrees  with  B.  enteritidis  i;i 
the  fermentation  of  this  substance.  This  divergence  was  brought  out  by  Krumvveicle 
et  al.'  We  have  been  helped  also  in  this  study  by  reference  to  the  work  of  Jordan,' 
and  preceding  articles  cited  here  and  that  of  Winslow,  Kligler  and  Rothberg.*  The 
Danysz  virus  and  paratvphoid  B.  were  from  the  U.  S.  Hygienic  Laboratory  and  th- 
B.  enteritidis  was  of  the'  Gaertner  type  and  came  from  Prof.  E.  O.  Jordan  in  1901. 

Five  cultures  of  B.  enteritidis-like  organisms  isolated  from  the  stools  of  influenza 
patients  by  Sherwood,  Downs  and  McXaught,'  were  sent  by  Dr.  Sherwood.  None  of 
these  agglutinated  with  M  5  antiserum. 


F.xpEKiMENTs  Showing  Th.vt  Broth   Clltlkus  oi 
WITH  which  .\x  .Axtitoxix  M.' 


.\I5   Cnxr.MX 
•  Be  PRonucED 


Plain  maltose  and  dextrose  beef  infusion  broths  were  tried.  It  was  found  that 
01%  dextrose  broth  (  +0.05)  yielded  the  most  potent  toxin,  .\fter  incubation  at  37  C. 
for  4-5  days  the  culture  was  filtered  through  a  Berkefeld  N.  The  filtrate  would  kill 
mice  in  12-18  hours  when  0.05-0.1  c.c.  was  injected  intraperitoneally.  Seventy  mice 
were  used  in  establishing  the  nature  and  potency  of  this  toxin.  Mice  dying  of  intoxica- 
tion showed  marked  injection  of  the  sulicutis  and  congestion  of  the  lungs.     Often  the 


of    Strains 

Para 

B.  Antiserum 

MS    Antiserum 

nesig.iation 

Simple 
Agglutination 

Homoloious 
AbsorteT 

Simple 
Agglutination 

Homologous 
*  Absorbed' 

M-5 

'.                    1                     .L 

Par.i    B 

1 

•i-                                         -f- 

I                    1                     l 

Med.  Res.,  1919,  39,  p.  AA9. 
Infect.   Dis.,   1920,  26,  p.  427. 
BactL-riol.,  1919,  4,  p.  429. 
Infect.   Pis.,   1920,  26,  p.   16. 


RAXSOHUFf  MEMORIAL  VOLUME 


pulmonarj-  congestion  bordered  on  consolidation.  The  In 
capillary  hemorrhages.  Other  organs  and  tissues  appcan 
We  found  that  about  2  c.c.  was  the  M  L  D,  on  in 
rabbit  weighing  1.800  gm.  By  inoculation  with  sublethal 
ing  the  amount  at  two-day   intervals,   over   a   period   of 


gs  often  showed 
normal  to  the  eye. 
avenous   inoculation,   for  a 
and  gradually  increas- 
eeks.  a   rabbit  could 


.I..S. 


tolerate  5  c.c.  of  a  freshly  prepared  toxin.  Eiglit  days  after  the  last  dose  of  toxin  the 
serum  of  this  rabbit  would  protect  mice  when  mixed  with  2  M  L  D  of  the  toxin  and 
at  once  inoculated  intraperitoneally. 

In  the  experiments  summarized  in  Table  7  the  vaccine  was  prepared  by  suspending 
an  agar  culture  in  0.9%  salt  solution,  heating  at  65  C.  for  si.xty  minutes  and  preserving 
with  0.5%  carbolic  acid.  The  density  was  somewhat  greater  than  that  of  a  24-honr 
broth  culture  of  B.  typhosus.  The  dosage  was  approximately  two  minims  for  each 
inoculation.  Several  tests  of  the  vaccine  before  and  after  its  use  showed  that  the 
bacilli  were  dead. 

TABLK  4 

The   MuuPiioLOGic  .^.^■n  CrLiLR.^i.  Ch.^r.«teristics  cr   M    .=;  anp  of   KtPKtsENT.M  ive   0»c.\nism» 

Selected  from   the   S.^me   Group 


Ml 
JJjjll) 


l  +  l  +  i  +  l— 1  +  .— I— I— I  +  lag'laglagl  — lag:— laglaglagl— aglagl— I— lag 

l  +  l  +  l  +  l  — !  +  l  — I  — I— I  -  lag   jaglagl  — lagl  — laglaglagj— aglagl— I— I— 

1  +  1  +  1  +  1  — 1  +  1— I  — I—  +  lag    aglag— jag!— jaglaglagl— aglagl— I— I— 

l  +  l  +  l  +  l— l  +  l — I— I— I  +  lag   laglagj  — lagl— laglaglagl— aglag;— 1— lag 


XPERIMENTS  Showing  th.^t  when  Ai 

Percentage   Develop  Pnei'Moni.\,   a 

Virus;  while  a   Spray    of    I 

AN     INFLI'I 


TABLE 

s  ARE  Exposed 


THE  Spray  of  M  5  Cultures  a  Large 
ILAR   Results   Follow   the   Spray   op   Danysz 
■48   Hours   Previously    from 

jt  effect 


Percentage 

Dale 

Aniina 

Is 

Number 
of 

Dead  Ani- 
mals with 
Prima 

^; 

ration  of 
ness   in 
Days 

Pvcmarks 

[   Pneumonia 

3/12/20 

4  mi 

1          4 

1 

I            100 

4-20 

1 
1 

3/17/20 

10  mi 

e 

1          8 

1            100 

4-15 

3/30/20 

^ 

1          4 

1             75 

1-10 

1  Sublethal    <lo«e    M  5    toxin 
1        given    few   hours   before 
!        spray.    One  lo.vin  death 

3/2.V20 

5  mi 

e 

1          4 

1            lOO 

4-12 

1 

4/  8/20 

se 

1          1 

If) 

! 

2   guinea 

pigs 

5/  5/20 

4  mi 

1         5 
1         0 

1            100 

12-20 

1   Danysz   virus   spray 
1   li.    influenzae 

TABLE  6 

ie  against  m  5  cultuk 
Doses  of   M  5   Soluble 


Date 

Number 
of  Mice 

Number          Duration 

of  Deaths  1      of  Illness     |                                     Remarks 
m  Days      i 

4/6/20 
4/6/20 

4/6/20 

4  1          3 

5  4 

4                    1 

11-18         1  One    (lose    soluble    toxing    6    days    before    spray 

12-44          1   Four    doses    soluble    toxin    at    3    day    intervals. 

Last   dose    5    days   before    exposure    to    spray 

14            1   Controls   without    toxin 

\ , 

WILLIAM  B.  WHERRY  AND  C.  T.  BUTTERflELD 


Subcutaneous 


Inoculation 


n.itc 

^"■■;|- 

N.nnl.er 
of  Deaths 

Percentage 
of  Dead 
Animals 

with 
Primary 

Pneumonia 

Dviralinn 
of  Illness 
in  IJnys 

1 

1                            KcKuks 

5/7/20 
5/7/20 
5/7/20 
5/7/20 

5 

3 
3 

5 

100 
33* 

66* 
80 

12-23 
1»-  8 

t  One  dose  10  days  before  exposure 
1        to  spray 

Two  doses  at  4  day  intervals.  Last 
1        dose    10    days    before    spray 

Three  doses  at  4  days  intervals. 
1  Last  dose  10  days  before  spray 
1    Controls    not    vaccinated 

•  Two  mice  died  of  general   infection   with  M  5  before  the 

Experiments  Showing  th.\t  Primary  Pneumonm 
JNI  5  Is  Inocul.M'Ed  by  Other  M 
When  tlie  portal  of  entry  was  through  the 
intestinal  mucosa,  the  suhcutis  or  peritoneal  ea\ 
two  cases  there  was  a  secondary  pneumonia.  In  : 
greatly  enlarged  and   full   of   whitish  ncemtic   or  pn 


xposure  to  the  spray. 

s  Not  PRonucED  in  Mice  When 
s  Than  Spr.^y 

iunrtna,  the  huccal  and  gastro- 
Keiicral  infection  followed.  In 
I  cases  tlie  liver  and  spleen  were 
ilifcrative  areas.      These  organic 


lesions  are  not  present  in  mice   dyini;  of   inhalation   pneumonia.     Placing  the  culture 
on  the  nasal  mucosa  was  without  effect. 

The  mice  fed  M  5  were  kept  without  food  and  water  for  from  1-2  days  and  then 
each  one  was  watched  while  it  lapped  up  the  drops  of  a  24-hour  broth  culture.  Those 
fed  heavily  ate  bread  soaked  with  the  broth  culture. 


TABLE  8 


IN    Mice   when    M  : 


Date 

Method   of 

Number 
of  Mice 

Number 
of  Deaths 

Percentage 

with  Pneu 

monia 

Duration 
of  Illness 
in  Days 

Remarks 

3/18/20 

Fed  heavily 

3 

0 

6-14 

1    Cen 

■ral   infection 

3/31/20 

Intraperi- 
toneal 

0 

2-4 

1 

ral  infection 

4/20/20 

Fed    1    drop 

1 

0 

8 

1,.'     ;   ilr.  I'.i-i 

4/20/20 

Fed    5    drops 

3 

10-18 

1     (.M 

4/20/20 

Fed  heavily 
Fed  heavily 

- 

12-17 

1    C.n 

"'"■ 

4/20/20 

,.il    nil\i.lHi]i 

5 /I  1  /20 

Subcutaneous 

3 

2-5 

1    Cen 

ral   infection 

5/11/20 

Ocular  con- 
junctiva 

50 

919 

1    Cen 

■ral     infection 

nonia 

5/11/20 

nares 

-1 

Experiments  Showing  Th.at  Spr.^ 

Diin-i 
(a)  Four  mice  and  one  unni.  ,i 
chloroformed  within  thirty  iiiiinilr 
were  wet  with  alcohol  and  jniiiu  i^,  i 
Then  they  were  dissert..!  villi  .,., 
pieces  of  the  lungs  ^l-^  iiini.  in  ili; 
planted  in  broth.  In  vyrw  iiT-laiii  e  , 
four  h.iiir-  Manv  ..f  \\u-  pie.<>.  ..i 
antcn..r    an. I    n..-!'.  n..r    I..1.,/.        I'n. 


ACTU.-\I.I 


Inh.m.ed   Into  the 


.1   u 


li  a  broth  culture  of  M  5,  and 
ning  of  the  experiment.  They 
rill  of  mercury  for  five  minutes, 
nd  from  each  animal  4-6  small 
ped  off  with  sterile  scissors  and 
ed  o-i-owth  of  M.s  within  twentv- 
'le  rxlrenie  .listal  |i.,rtions  of  the 
ii'.K    wire    ireate.l    m    the    same 


RAXSOHOFF  MEMORIAL  VOLUME 


Attempts  to  Produce  Pneumonia  in  ^ficE  by  Spraying  Pneumococci 

Having  shown  that  sprayed  bacteria  reach  the  deepest  alveoli,  or  capillary  bronchi, 
of  the  lungs  and  that  pneumococci  planted  in  this  way  survive  in  the  lungs  of  mice 
for  at  least  eighteen  hours,  the  maximum  period  tested,  we  made  the  following  experi- 
ments with  a  type  1  pneumococcus.  This  culture  had  been  kept  highly  virulent  for 
mice  at  the  United  States  Hygienic  Laboratory. 

Four  mice  were  sprayed  with  the  growth  from  four  blood  agar  slants  suspended 
in  broth.  They  were  exposed  for  thirty  minutes.  Two  died  of  primary  lobar  pneu- 
monia in  fourteen  days.  No  bacteria  could  be  found  in  the  purulent  exudate  and  all 
cultures  remained  sterile.  The  remaining  two  were  killed  six  weeks  later.  They 
appeared  normal  and  cultures  from  the  lungs  remained  sterile. 

The  mice  were  kept  at  8  C.  for  four  hours  and  then  sprayed.  They  felt  warm 
on  removal  from  the  icebox.  Two  were  killed  and  cultured  shortly  after  spraying. 
Pneumococci  grew  out  of  all  pieces  of  their  lungs,  including  the  most  distal  portions. 
At  the  cml  of  four  weeks  the  remaining  eight  mice  were  chloroformed  and  cultured 

with  i)^■^.l[l\r    rr~\\]\<. 

Siiic^'  M  5  ^  'liiMc  toxin  injures  the  lungs  of  mice,  six  mice  which  bad  survived 
sublctlial  (Insts  (if  this  toxin  given  ten  days  before  were  sprayed.  They  were  killed 
si.x  weeks  later  and  fmnid  normal.     Xor  did  they  harlmr  pneumococci. 

Four  mice  were  given  Mililethal  doses  of  M5  toxin  ami  sprayed  with  pneumococci 
at  once.  Six  weeks  later  one  of  these  mice  died  of  pneumonia  caused  by  M5:  no 
pneumococci  could  be  found.  The  remaining  three  were  killed  and  cultured  eight 
weeks  lalcr.     Thc\    were  normal  and  the  cultures  remained  sterile. 

Three  mice  were  sprayed  with  the  pneumococcus  and  then  in  an  attempt  to  give 
them  an  acidosis  they  were  kept  under  ether  for  one  hour.  One  of  these  was  further 
chilled  in  ice  water  for  ten  minutes.  They  survived  and  yielded  no  growths  four 
weeks  later. 

Two  mice  were  sprayed  with  a  broth  suspension  of  bloody  sputum  from  a  case 
of  pneumococcus  loliar  pneumonia.    They  remained  well  during  six  weeks'  observation. 

Since  none  of  tlie  t\vent_v-nine  mice  became  infected  after  inhaling  viru- 
lent pnetmiococci  into  their  lungs,  one  ma}-  conclude  that  some  predisposing 
factor  must  precede  or  accompany  such  an  implantation  of  bacteria.  While 
we  owe  the  whole  idea  of  droplet  infection  to  Fliigge  and  his  pupils  and 
confess  that  we  have  relied  on  the  review  of  their  work  by  Goetschlich," 
we  are  not  aware  of  the  fact  if  these  workers  demonstrated  that  bacteria 
are  to  be  recovered  from  the  deepest  portions  of  the  lungs  of  sprayed 
animals.  Our  attention  was  drawn  to  this  by  Rogers,"  who  showed  that 
tubercle  bacilli  could  be  recovered  from  the  lungs  of  guinea-pigs  immedi- 
ately after  spraying  them  with  tuberculous  sputum,  and  that  such  protected 
and  sprayed  animals  develop  true  primary  pulmonary  tuberculosis. 

We  are  familiar  with  the  work  of  Diirck,^  who,  by  means  of  intra- 
tracheal insufflation,  was  unable  to  infect  the  lungs  of  rabbits  with  freshly 
isolated  cultures  of  pneumococcus,  streptococcus  pyogenes,  and  staphylo- 
coccus ain-eus  unless  at  the  same  time,  or  before  or  after,  injurious  dust 
particles,  pumice,  or  "Thomasphosphatmehl"  were  also  blown  into  the  lungs. 
This  sterile  dust  alone  produced  pneumonia  while  sterile  street  dust  did  not. 
He  also  describes  the  production  of  typical  pneumonia  in  rabbits,  with 
secondary  invasion  of  the  pneumonic  areas  by  B.  coli,  sarcinae,,  or  Fried- 
lander's  bacillus,  by  keeping  them  at  37-41  C.  for  sixteen  to  thirty-six 
hours  and  then  in  ice  water  for  two  to  seven  minutes. 

«  H.in<ll,lich   (1.   l);Ul).   Miki-oorg..   Kolle  :iml  Wasse.  n.ann,    IVN,    \„l.    J. 
'  .Ann-r.   Utv.  Tiiljcrc.   1919.   3.  p.   -'.>».  and   1920.  1.   p.   7.S0. 
'  Dcut,   .\rch.   f.   kliii.    Med,.    1897.   58,  \,.  308. 


WILLIAM  B.  WHERRY  AND  C.  T.  BUTTERFIELD 

However,  these  experiments  and  those  made  by  the  method  of  intra- 
bronchial  insufflation,  which  was  introduced  by  Lamar  and  Meltzer  and 
used  by  many  others,  do  not  appeal  to  us  as  represnting  what  must  take 
place  under  natural  conditions.  Bacteria  can  be  inhaled  into  the  deepest 
parts  of  the  lungs  and  if  they  are  capable  of  multiplying  there  they  will 
produce  pneumonia,  as  in  the  case  of  M  5.  The  fact  that  virulent  pneu- 
mococci  do  not  multi]:)ly  when  planted  in  the  lungs  of  mice  by  air  currents 
is  an  interesting  fact  and  deserves  further  investigation. 

SUMMARY  .\XD  CONCLUSIONS 

When  white  mice,  white  rats  and  guinea-pigs  were  exposed  to  finely 
divided  influenza  s])utum  sprays  some  died  of  a  primary  pneumonia,  others 
of  a  general  infection  due  to  a  .strain  of  B.  enteritidis  (type  M  5).  Since 
the  work  of  others  has  shown  that  these  animals  may  die  of  spontaneous 
infection  with  members  of  the  paratyphoid-enteritidis  group  we  can  not 
say  that  these  infections  were  necessarily  the  sequel  to  the  spray.  How- 
ever, as  primary  pneumonia  could  not  be  produced  in  mice  when  M  5  was 
inoculated  through  the  buccal  or  gastro-intestinal  mucosa,  the  conjunctiva, 
subcutis  or  peritoneal  cavity,  but  only  when  sprayed,  it  seems  to  us  likely 
that  something  in  the  sputum  sprays  produced  a  change  in  the  pulmonary 
tissues  favoring  such  secondary  localization. 

Broth  cultures  of  M  5  contain  a  soluble  toxin  which  produces  marked 
congestion  of  the  subcutaneous  and  pulmonary  tissues  of  white  mice.  This 
toxin  gives  rise  to  an  antitoxin  when  injected  into  rabbits.  Previous  inocu- 
lation with  the  toxin  did  not  produce  immunity  to  the  development  of  pri- 
mary pneumonia  by  sprayed  cultures,  nor  were  we  able  to  immunize  against 
the  spray  of  M  5  cultures  by  previous  subcutaneous  inoculations  with  a 
dead  culture. 

The  intoxication  of  mice  with  the  soluble  toxin  or  with  killed  cultures 
of  M  5  apparently  led  to  infection  with  M  5  in  a  small  percentage  of  the 
used  mice.  We  were  not  able  to  find  this  bacterium  in  normal  mice,  nor 
did  spraying  mice  with  virulent  pneumococci  make  it  show  itself  as  a 
secondary  invader. 

Experiments  show  that  AI  5  and  virulent  pneumococci  are  inhaled  by 
mice  into  the  deepe.st  alveoli  or  capillary  bronchi  of  the  lungs,  and  that  pri- 
mary pneumonia  follows  in  the  case  of  M  5,  which  is  capable  of  growing 
and  producing  its  toxins  there,  whereas  the  virulent  pneumococci  gradually 
disappear. 


THE   PRIXCIPLES   OF  TREATMENT   IX   MERCTRIC   CHLORID 

POISONING 

WITH  RESULTS  OF  TREATMENT* 

H.  B.  Weiss.  M.D., 

Cincinnati. 

Within  the  past  two  years  there  has  been  much  work  done  in  the  vari- 
ous phases  of  mercuric  chlorid  poisoning.  Before  then,  most  of  the  work 
reported  was  of  a  therapeutic  nature ;  but  recently  new  and  important 
laboratory  data  have  been  contributed.  These  new  data  have  certainly  put 
the  modern  therapeutic  measures  to  the  test,  discrediting  many  and  placing 
a  few  on  a  firm  basis. 

The  anatomic  pathologj'  has  been  well  established.  E\cry  organ  of 
the  body  is  affected,  the  liver  and  kidneys  bearing  the  brunt  of  the  injuries. 
From  a  cloudy  swelling  the  changes  continue  to  fatty  degeneration  and 
necrosis.  When  the  poisoning  is  severe,  hemorrhagic  inflammation  may 
supervene. 

Schamberg,  Kolner  and  Raiziss,^  in  their  studies  of  the  comparative 
toxicity  of  the  various  preparations  of  mercury  used  for  therapeutic  pur- 
poses, have  shown  in  a  long  series  of  dogs  that  every  animal  develops  evi- 
dences of  nephritis  of  varying  degrees  after  injections  of  both  the  soluble 
and  insoluble  mercury  salts.  The  nephritis  produced  is  primarily  tubular, 
with  frequent  accompanying  glomerulonephritis  (hemorrhagic)  in  the  se- 
verer instances.  The  changes  in  the  tubular  epithelium  they  attribute  to  a 
direct  toxic  degeneration  of  the  cells  by  the  mercury,  and  not  to  an  inflam- 
matory reaction  depending  on  the  elimination  of  toxic  substances. 

Mercury  has  been  obtained  from  the  blood  of  dogs  within  ten  minutes 
after  its  administration  by  mouth.-  Burmeister  and  McNally  have  shown 
that  the  kidney  changes  vary  with  the  size  of  the  dose  in  massive  intoxica- 
tion, and  that  the  liver  changes  depend  on  the  duration  of  the  intoxication. 

The  im])ortant  newer  studies  consider  the  fpiestion  from  a  chemical 
standpoint.  It  is  from  tliis  point  of  view  that  the  present  treatment  must 
be  evolved. 

.■\s  tlic  mercury  is  cjuickly  taken  up  by  the  blood  after  ingestion,  it  is 
evident  that  all  the  tissues  are  quickly  bathed  with  the  toxic  material.  In  a 
fatal  case  of  mercury  poisoning,  it  was  found  that  almost  one-third  of  the 
mercury  recoverable  from  the  body  was  obtained  from  the  blood. ^    In  1916, 

•  From  the  Department  of  Medicine,  University  of  Cincinnati  College  of  Medicine,  and  the 
Medical  Clinic,  Cincinnati  General  Hospital. — From  the  Journal  of  the  .American  Medical  Associa- 
tion,   September,    1918. 

"Schamberg,  J.  F..  Kolmer,  J.  A.,  and  Raiziss,  G.  M.:  A  Study  of  the  Comparative  Toxicity 
of  the  Various  Preparations  of  Mercury,  Jour.   Cutan.   Dis.,    1915,   33,   819-8J0. 

•Burmeister,  VV.  H.,  and  .McNally,  W.  1).:  Mercury  Poisoning,  Jour.  Med.  Research.  1917.  3(<. 
87. 

the    liody   in   a   Case   of   Acute 


H.  B.  WEISS 


Lewis  and  Rivers*  found  that  the  retention  of  waste  nitrogen  was  a  factor 
in  the  production  of  early  fatalities.  More  recently  MacNider/  in  an  ex- 
haustive study,  has  demonstrated  some  essential  facts.  Those  animals  that 
did  not  succumb  from  the  early  gastro-enteritis  developed  a  severe  type  of 
acid  intoxication,  as  evidenced  by  the  production  of  acetone  bodies,  the  re- 
duction of  the  alkali  reserve  of  the  blood,  and  the  increase  in  carbon  dioxid 
content.  Constantly  associated  with  this  acid  intoxication  was  a  kidney  in- 
jury. He  states  that  delayed  kidney  injury  is  not  due  to  the  action  of  the 
mercury  as  such  during  its  elimination  by  this  organ.  He"  had  previously 
shown  that  acetcjiie  and  diacetic  acid  are  developed  in  nephritis  produced 
by   uranium,  and   that   administration   of   alkaline   carbonates   lessened    the 


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toxicity  of  the  tu-anium  and  delayed  the  formation  of  the  acid  bodies. 
Furthermore,  when  the  kidney  was  protected  by  carbonate,  it  was  found 
that  the  kidney  remained  functionally  more  active,  and  that  there  was  a 
diminished  acute  swelling,  fatty  degeneration  and  necrosis  of  the  renal 
epithelium. 

It  is  this  work  which  has  proved  correct  the  therapeutic  principles 
that  I  have  em])loyed  in  the  treatment  of  mercuric  chlorid  poisoning.' 

The  symptoms  of  poisoning  by  mercury  are  well  known :  locally  burns, 
and  later  vomiting  and  gastro-intestinal  hemorrhages ;  as  the  toxemia  prog- 
resses, oliguria,  then  anuria  and  finally  "uremic"  .symptoms,  as  convulsions 
and  death. 

Many  remedies,  empiric  and  allegedly  scientific,  have  been  advocated 
in  the  use  of  mercury  poisoning,  but  they  seem  not  to  have  stood  the  test 


1  a  Case  of  Bictiloride  Poisoning,  Johns 
Clilorid    Intoxication    in    tlie    Dog    with 


'  .M-icXuicr,  V\.  ,1c  K.;  Tlic  liil 
bonate.  and  the  Protection  of  the  Kidn 
of  an   Anesthetic  by    Sodium   Carhonal 

'Weiss,  H,  B.:  .\  Method  of  Tr< 
June  2,    1917,   p.   1618;   The  Tr 


1917 


13,  597. 


RAXSOHOFF  MFMORIAL  VOLUMF 


of  time,  ^^'e  have  used  tlie  alkaline  treatment  for  more  than  three  years, 
and  our  records  show  a  lower  mortality  than  that  ordinarily  reported. 

The  principle  involved  in  the  use  of  alkali  is  that  of  trying  to  counteract 
the  acid  intoxication  produced,  which  in  turn  produces  the  generalized 
toxemic  swelling  and  degeneration  of  all  the  body  tissues.^  When  there  is 
present  oliguria,  with  blood  and  casts  in  the  urine,  we  have  evidences  of 
acute  kidney  injury.  This  discernible  kidney  injury  is  merely  an  indication 
of  an  injury  common  to  all  the  body  tissues,  for  we  know  that  the  entire 
organism  has  been  bathed  by  the  mercury.  The  alkali  is  not  given  as  an 
eliminant,  but  to  counteract  acid  intoxication,  edema  and  cloudy  swelling, 
which,  if  permited  to  go  on,  proced  to  fatty  degeneration  and  irreversible 
cell  damage  (necrosis). 

Sansum,"  in  a  recent  paper,  seems  to  believe  that  the  basis  for  the  use 
of  alkali  is  to  be  found  in  its  power  to  increase  diuresis  with  a  secondary 
washing  out  (increased  elimination)  of  mercury.  Because  he  finds  no  in- 
creased mercury  elimination,  he  leads  his  readers  to  suppose  that  the  use 
of  alkali  as  a  therapeutic  agent  is  valueless.  The  alkali,  however,  is  not 
used  solely  for  its  eliminatory  action,  but  to  inhibit  and  to  counteract 
damage  to  the  tissues  which  mercury,  if  left  to  itself,  produces. 

At  present  we  can  report  on  fifty-four  consecutive  cases  of  mercurial 
poisoning  with  but  three  deaths.  Of  the  three  patients  that  died,  two  re- 
ceived the  treatment  only  after  unavoidable  delay,  and  one  had  a  pre- 
existing ne])hritis  and  cirrhosis. 

METHOD  OF   TKF.ATMEXT 

Essentially  the  treatment  which  I  have  jiroposed  consists  of  an  early 
washing  out  of  the  mercury  salt  from  the  stomach  and  intestine  and  con- 
tinued introduction  of  sufficient  alkali  to  overcome  the  acid  intoxication. 

The  patient  should  come  under  observation  as  early  as  possible,  for  I 
have  found  that  when  the  treatment  is  delayed  for  any  reason,  the  symp- 
toms produced  by  the  mercury  poisoning  become  more  difficult  to  control. 
Two  patients  of  my  series  died,  I  think,  because  treatment  was  commenced 
too  late. 

I  usually  wash  out  the  stomach  with  a  mixture  of  one  quart  of  milk 
and  the  whites  of  three  eggs,  following  this  by  a  saturated  solution  of  so- 
dium bicarbonate  until  the  stomach  washings  return  clear.  Finally,  before 
the  stomach  tube  is  removed,  from  three  to  four  ounces  of  crystallized 
magnesium  sulphate  dissolved  in  from  six  to  eight  ounces  of  water  are 
allowed  to  remain  in  the  stomach.    A  .soap  suds  enema  is  then  given. 

Usually  the  i)atient  vomits  shortly  after  taking  the  mercury,  thereby 
aiding  in  the  elimination  of  the  poison. 

The  next  step  is  to  introduce  alkali,  and  we  give  the  alkali  by  mouth, 
rectum  and  intravenously.    As  soon  as  possible  after  washing  the  stomach, 

•  Fischer,  M.   H.:    Edema  and  Nephritis,   New  York,  John   Wiley  &   Sons.   1915. 
•Sansiim.   W.    D. :     The   Principles   of   Treatment    in    .Mercuric    Chlorid    I'oisoning.    The    luiirnal 
.\.   M.   .\.,   March  23,   1918,  p.  824. 


H.  B.  WEISS 


the  patient  is  given  Fischer's  solution  intravenously.  Fischer's  solution 
consists  of  crystallized  sodium  carbonate,  10  gm.  ( NaXO,,10H;O)  (or 
4.2  gm.  of  the  ordinary  "dry"  salt)  ;  sodium  chlorid.  15  gm.,  and  distilled 
water.  1.000  c.c. 

Depending  on  the  state  of  the  circulatory  system,  from  1,000  to  2.000 
c.c.  of  the  solution  are  given  intravenously  as  a  first  dose.  We  continue 
the  alkaline  medication  by  giving  eight  ounces  of  "imperial  drink"  every 
two  hours.  This  drink  consists  of:  potassium  bitartrate  (cream  of  tartar), 
4  gm.  (one  teaspoonful)  ;  sodium  citrate,  2  gm.  (one-half  teaspoonful)  ; 
sugar,  2  gm.    (one-half  teaspoonful),  and  water,  240  c.c.    (eight  ounces). 

This  drink  is  flavored  with  lemon  or  orange  juice.  The  patient  is 
allowed  large  quantities  of  it. 

There  is  no  restriction  in  diet  at  any  time  during  the  treatment. 

As  an  indication  of  the  severity  of  the  acid  intoxication,  and  as  a  guide 
to  the  amount  of  alkali  and  salt  that  needs  to  be  given,  we  use  the  analysis 
of  the  urine.  Except  in  suppression  cases  (which  were  rare  in  our  series), 
the  patient  voids  large  quantities  of  urine,  the  amounts  depending  on  the 
amount  of  fluid  taken.  The  urine  should  become  alkaline  to  methyl  red 
(a  saturated  solution  of  methyl  red  in  alcohol)  and  be  kept  so,  for  Fischer 
has  demonstrated  that  if  the  urine  of  a  nejjhritic  can  not  be  maintained 
alkaline  to  methyl  red,  the  patient  continues  in  a  serious  state.  If  the  out- 
put of  urine  is  not  seen  to  be  maintained,  and  if  its  reaction  does  not  be- 
come alkaline  to  methyl  red  after  the  first  intravenous  injection,  a  second 
intravenous  injection  is  given  the  following  day,  and  general  alkali  admin- 
istration by  mouth  or  rectum  is  continued. 

RESULTS 
Under  this  treatment,  there  is  usually  produced  and  maintained  a  free 
secretion  of  urine  which  remains  alkaline,  and  an  output  of  albumin  in  the 
urine,  which  usually  develops  early,  rapidly  disappears.  Ordinarily  two 
intravenous  injections  of  the  alkali,  together  with  the  solution  of  potassium 
bitartrate  and  sodium  citrate,  which  is  given  at  hourly  or  two  hourly  in- 
tervals, day  and  night  (when  the  patient  is  not  asleep)  has  been  found 
sufficient  to  keep  the  urine  alkaline  and  to  keep  the  output  of  urine  normal. 
The  blood  and  casts  in  the  urine  are  usually  quickly  dissipated.  Tiie  pa- 
tient is  kept  under  observation  for  about  ten  days  after  the  urine  has  be- 
come normal,  and  is  then  discharged. 

•  I  have  shown  previously"  that  patients  treated  early  show  fewer  symp- 
toms and  make  a  more  rapid  recovery  than  those  in  whom  treatment  is 
delayed. 

Page  567 


RAXSOHOI'l-  MllMORlAL  VOLUME 


We  have  performed  phenolsulphonephthalein  tests  on  most  of  our  pa- 
tients, and  it  is  interesting  to  note  that  those  who  were  treated  early 
showed  only  slight  or  no  diminution  in  phenolsulphonephthalein  output. 
When  the  output  was  diminished,  it  rapidly  rose  to  normal  and  continued 
so.  In  one  patient  who  developed  an  anuria  for  three  days,^"  the  phenol- 
sulphonephthalein output  was  practically  zero  for  five  days  after  he  com- 
menced to  void,  and  then  rapidly  rose  to  66  per  cent,  (as  shown  in  the  ac- 
companying chart)  at  the  end  of  thirty-three  days.  This  patient's  urine 
was  normal  six  months  after  his  recovery  from  the  mercuric  chlorid  poison- 
ing. 


THE  \'ENEREAL  PROBLEM. 
PiTiLip  Zkxnf.r,  A.m.,  M.D.. 

Cincinnati. 

My  subject  is  the  venereal  prolilein  ;  that  is.  the  problem  of  the  prevention 
of  the  venereal  disease.  This  is  no  new  problem.  Many  years  ago,  a  great 
American  surgeon  e.xpressed  the  fear  that  these  diseases  would  lead  to  the 
deterioration  of  the  whole  human  race. 

Have  these  diseases  been  on  the  increase  as  this  fear  suggests?  \\'e 
have  no  data  which  enal>le  us  to  give  a  definite  answer  to  this  question,  but 
there  is  much  which  gi\es  that  appearance. 

When  I  was  a  student,  jiaresis  and  locomotor  ataxia  (I  suppose  that  you 
know  that  they  are  due  to  syphilis)  were  rarely  found.  Today  we  see 
I  hem  frequently.  But  we  know  much  more  about  these  diseases  than  we 
did  in  those  days,  and,  therefore,  more  readily  recognize  them,  and  this 
may  be  the  full  explanation  of  their  apparent  greater  frequency. 

Then  we  have  a  new  test  of  syphilis,  a  blood  test — the  Wassermann 
test — which  enables  us  to  find  the  disease  in  many  cases  where  it  would 
otherwise  have  gone  unrecognized.  We  have  also  a  new  test  for  gonor- 
rhea, so  that  now  we  know  that  gonorrhea  is  common  in  women  and  chil- 
dren, of  which  fact  we  were  not  formerly  aware.  In  women  the  disease 
often  leads  to  confirmed  invalidism  and  is  a  common  cause  of  sterility  ; 
in  children  it  often  causes  blindness. 

These  facts  do  not  prove  that  venereal  diseases  are  on  the  increase, 
but  they  have  aroused  the  world  to  a  knowledge  of  their  prevalence  and 
their  danger.    The  problem  became  acute  when  we  entered  the  war. 

War  always  has  increased  the  venereal  diseases.  They  spread  rapidly 
in  armies  and  after  the  war  the  soldiers  spread  them  among  the  people. 
That  was  the  experience  of  this  war.  In  some  of  the  European  armies 
these  diseases  disabled  more  soldiers  than  did  shot  and  shell.  Their  effect 
was  equivalent  to  the  wiping  out  of  whole  army  corps,  and  since  the  war 
the  disease  has  played  havoc  with   some  of   the  European  peoples. 

The  knowledge  of  such  facts  led  our  government,  when  we  entered  the 
war,  to  take  rigid  measures  to  prevent  the  spread  of  the  venereal  diseases 
in  our  army.  These  measures  were  phenomenally  successful.  Let  us 
briefly  review  them : 

First,  the  soldier  was  kept  bu.sy  and  thereby  out  of  mischief;  during  his 
work  hours,  busy  with  his  training;  during  his  hours  of  leisure  he  was 
given  wholesome  entertainment. 

Secondly,  he  was  forbidden  alcoholic  drinks  and  houses  of  prostitution 
were  banished  from  his  neighborhood. 

Thirdly,  he  was  given  sex  instruction  by  means  of  pamphlets,  moving 
pictures,  talks  from  his  ofificers  and  special  lectures.  He  learned  that  con- 
tinence is  altogether  consonant  with  health  and  vigor,  whereas  he  had  pre- 
viously been  taught  that  sexual  indulgence   was  a  necessity.     He  learned 


RANSOHOFF  MFMORIAL  VOLUME 


that  not  only  \\as  syphilis  a  disease  he  already  dreaded,  a  grave  disease,  but 
that  gonorrhea,  a  disease  he  had  been  accustomed  to  look  upon  lightly,  was 
also  grave,  sometimes  worse  than  syphilis.  This  is  especially  true  because 
of  its  complications.  For  instance,  10  per  cent,  of  the  cases  of  gonor- 
rhear  in  our  army  had  gonorrheal  rheumatism,  the  worst  form  of  rheuma- 
tism. He  learned  also  that  a  man  may  believe  himself  to  be  well  while 
the  disease  is  still  lurking  in  his  system  and  mav  later  infect  his  wife  and 
children.  'I'his  sex  instruction  had  a  decided  influence  ujion  the  soldier's 
conduct. 

Finally  there  is  the  measure  we  term  ]mjphylaxis,  preventixe  treatment 
in  case  the  individual  exposes  himself  to  infection.  This  consisted  usually 
of  urethral  injection  of  a  2  per  cent,  silver  solution  and  an  external  appli- 
cation of  a  mercurial  salve.  The  order  was  imperative  that  the  soldier 
have  this  treatment  in  case  of  exposure.  To  see  that  the  order  was  enforced 
the  soldier  was  examined  at  least  twice  a  month,  and  if  disease  were  found 
and  he  had  not  previously  apjilied  for  treatment  he  was  court-martialled 
and  severely  punished. 

As  I  said,  these  measures  were  phenomenally  successful.  As  Surgeon- 
General  Blue  expressed  it,  "The  venereal  rate  was  lowered  below  that  of  any 
army  of  any  nation  in  the  history  of  the  modern  world."  But  even  then  the 
venereal  disease  in  our  army  was  by  no  means  an  insignificant  matter.  It 
was  still  the  most  disabling  single  factor,  in  truth  more  disabling  than  all 
other  acute  diseases  together,  leaving  out  influenza  and  measles.  Some 
figures  will  give  you  an  idea  of  this.  One  week  when  I  had  occasion  to 
look  up  the  records  of  Camp  Sherman,  there  were  1,700  patients  in  the 
hospital,  and  of  this  number  800  were  cases  of  venereal  disease.  Between 
September,  1917,  and  September,  1918,  there  were  170,000  cases  of  venereal 
disease  in  our  army.  But  I  would  not  have  these  figures  mislead  you  as 
to  the  efliciency  of  the  campaign  against  these  diseases.  Only  in  the  smaller 
number,  about  one-sixth  of  these  cases,  was  the  disease  contracted  after 
the  soldiers  entered  the  army.  In  the  larger  number,  about  five-sixths, 
the  disease  was  contracted  before  they  entered  the  service ;  it  was  acquired 
in  civil  life. 

'J'his  brings  us  to  the  problem  we  have  before  us  today — what  can  be 
done  to  prevent  the  disease  in  civil  life.  Let  us  again  consider  a  few  of  the 
measures  so  efYective  in  the  army,  and  first  the  suppression  of  houses  of 
prostitution.  This  measure  was  very  effective  in  the  army.  To  illustrate 
this  fact  I  will  mention  the  e-xjierience  of  an  army  corps  in  the  French 
corps  in  the  French  |3ort,  v^aint  Xezaire.  where  ])rostitution  flourished. 
Before  the  division  reached  this  port  its  disease  had  been  reduced  to  the 
low  annual  rate  of  fifty-four  per  thousand.  In  Saint  Nazaire  the  rate  soon 
rose  to  two  hundred  and  one.  When  this  was  observed,  the  houses  of 
prostitution  were  put  bcvond  the  soldiers'  reach  and  the  rate  fell  markedly 
at  once. 


Page 


FHILIP  ZENNER 


We  could  not  expect  an  equal  effect  in  civil  life  where  there  is  neither 
the  same  discipline  nor  the  same  control,  but  still,  good  must  come,  if  only 
from  the  physical  possibilities.  A  woman  in  a  house  of  prostitution  some- 
times has  contact  with  fifty  men  or  more  in  twenty-four  hours,  whereas 
if  she  must  seek  her  prey  on  the  street  she  can  not  find  nearly  as  many 
victims. 

And  now  as  to  prophylaxis.  That  had  a  great  eft'ect  in  the  army.  Some 
figures  again  will  make  this  clear  to  you.  In  one  division,  where  the  matter 
was  carefully  studied,  it  was  found  that  of  those  who  had  received  prophy- 
laxis only  one  in  ninety  contracted  the  disease,  whereas  one  in  thirty  be- 
came infected  where  this  treatment  was  not  applied — a  reduction  of  662;:j 
per  cent.  Nevertheless,  it  is  very  unlikely  that  this  measure  will  lessen  the 
prevalence  of  the  disease  in  the  community,  and  this  for  two — people  will 
not  apply  for  it,  and  the  time  they  would  apply. 

Army  experience  throws  light  upon  this  statement.  In  our  own  army, 
notwithstanding  the  severe  punishment  inflicted  if  the  soldier  did  not  apply 
for  the  treatment  after  exposure,  from  one-fourth  to  one-third  of  the  men 
failed  to  do  so.  The  report  of  a  British  surgeon  is  still  more  illuminating. 
According  to  his  report,  the  treatment  was  a  voluntary  matter  with  the 
soldiers,  but  they  were  offered  every  facility  for  its  application,  and  yet 
not  one  among  some  thousands  of  men  made  use  of  it.  In  civil  life,  where 
secrecy  is  usually  desired,  there  would  be  still  less  likelihood  of  the  in- 
dividual seeking  the  treatment. 

As  to  time,  the  usual  experience  has  been  that  when  the  treatment  is 
applied  immediately,  or  within  an  hour,  after  intercourse,  it  is  almost  in- 
variably successful,  but  that  after  a  number  of  hours  has  elapsed  it  is  use- 
less. This  brings  up  the  question  of  self-treatment,  the  individual  being 
supplied  with  the  necessary  remedies  and  applying  them  himself  immedi- 
ately after  intercourse.  If  this  procedure  were  a  common  one  there  is 
no  doubt  that  it  would  increase  rather  than  diminish  the  amount  of  ve- 
nereal disease,  for  usually  it  would  be  applied  imperfectly  and  be  no  source 
of  protection  while  the  sense  of  security  given  would  lead  many  into 
danger  which  they  would  otherwise  have  shunned.  There  is  extended 
experience  in  demonstration  of  the  truth  of  this  statement.  Before  the 
war  this  mode  of  treatment  was  in  vogue  in  our  navy  and  it  was  also  tried 
in  the  New  Zealand  expeditionary  force  in  France.  In  both  instances  it 
proved  to  be  a  failure. 

I  have  spoken  so  fully  of  i>rophylaxis  liecause  there  are  those  who  be- 
lieve that  it  is  the  means  of  the  control,  if  not  the  eradication,  of  these 
diseases,  whereas  unless  the  facts  I  have  given  you  are  altogether  mislead- 
ing, we  can  expect  little  or  nothing  in  this  way. 

Our  government  did  not  discontinue  its  campaign  against  the  venereal 
diseases  when  it  discharged  its  soldiers.  Each  year  since  the  war  Congress 
has  appropriated  $2,000,000  for  this  purpose.    This  money  is  divided  among 

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RAXSOHOFf  MEMORIAL  VOLUME 


the  states,  which  will  provide  an  amount  equal  to  that  given  them,  and  now 
in  forty-seven  states  this  campaign  is  carried  on.  the  national,  state  and 
local  health  authorities  working  together.  So  far  their  effort  has  been  de- 
voted chiefly  to  finding  and  curing  existing  cases  of  disease.  \'enereal  dis- 
ease is  very  contagious.  It  is  catching  from  person  to  person.  If  every 
case  could  be  cured  there  would  be  no  further  source  of  contagion  and  the 
disease  would  vanish  from  the  earth.  This  is  a  practical  impossibility,  but 
lo  the  extent  that  cases  are  cured  is  the  prevalence  of  the  disease  lessened 
or  at  least  its  increase  diminished. 

One  of  the  greatest  obstacles  to  finding  and  curing  cases  of  the  disease 
is  the  quack  and  quack  nostrums.  The  only  object  of  the  quack  is  to  make 
money,  and  to  do  so  he  deceives  the  people.  His  treatment  is  likely  to  be 
inadequate  and  he  is  likely  to  lead  his  patient  to  believe  that  he  is  well, 
while  the  disease  still  lurks  in  his  system  with  all  its  possibilities  of  harm. 
Durng  the  war.  when  man  power  was  of  vital  importance,  England  severely 
punished  quacks  who  treated  venereal  diseases.  One  of  our  states,  Ala- 
bama, recently  enacted  a  law  forbidding  the  advertising  of  quack  venereal 
doctors  and  the  advertisement  and  sale  of  quack  venereal  remedies.  Many 
of  the  best  newspapers  in  the  land  w-ill  not  accept  any  medical  advertise- 
ments. But  to  really  escape  the  danger  of  the  quack,  the  people  must  have 
a  full  understanding  of  the  matter.  They  must  know  that  the  quack  is  a 
source  of  harm,  whatever  disease  he  pretends  to  cure,  and  though  he  be 
graduated  physician,  that  he  deceives  the  people,  that  he  plays  upon  their 
their  fears  and  often  falsely  arou.ses  fear,  that  every  advertising  medical  man 
is  a  quack  and  most  advertised  medicines  quack  nostums. 

One  of  the  great  purpo.ses  of  this  national  campaign  is  to  tell  about  the 
quack.  Another  measure  is  the  establishment  of  free  clinics  for  the  treat- 
ment of  those  unable  to  pay.  Here  they  are  given  the  most  modern 
methods  of  treatment  and  are  urged  to  continue  the  treatment  until  they 
are  quite  well.  Also  lectures  are  given  to  the  people  in  factories  and 
many  other  places.  The  lectures  aim  to  tell  about  the  venereal  diseases, 
their  danger,  their  contagiousness,  and  the  great  need  of  avoiding  them. 
They  also  urge  the  diseased  to  go  only  to  competent  men  for  treatment 
and  to  remain  under  treatment  until  cured  and  no  longer  a  danger  to  others. 

Many  laws  have  been  enacted  to  help  along  this  campaign.  Most 
states  require  that  physicians  report  all  their  cases  of  venereal  disease. 
This  is  essential  if  the  campaign  is  to  be  successful,  for  there  can  scarcely 
be  a  sucessful  fight  against  a  disease  without  some  idea  of  its  degree  of 
prevalance.  Many  states  require  physicians  to  hand  their  patients  printed 
instructions  how  to  avoid  giving  the  disease  to  others,  and  if  these  instruc- 
tions are  not  heeded  health  authorities  have  the  power  to  quarantine  the 
patient.  Many  states  have  made  so-called  eugenic  laws,  laws  to  control 
marriage,  to  forbid  the  marriage  of  infected  individuals. 

There  is  a  great  difference  between  making  laws  and  enforcing  them. 
Certainly  it  is  a  difficult  matter  to  get  physicians  to  report  their  cases, 
Paijc  .r.z 


PHILIP  ZENNER 


almost  the  foundation-stone  of  this  whole  structure,  ^^'e  cannot  tell  of 
the  future,  but  we  can  say  that  the  full  success  of  this  campaign  will  de- 
pend upon  national,  state  and  local  health  officials,  as  well  as  physicians 
and  voluntary  associations  established  for  the  purpose,  working  together 
and  upon  an  informed  and  sympathetic  public  sentiment. 

The  question  arises  whether  this  campaign,  now  going  on  nearly  two 
years,  has  lessened  the  cases  of  venereal  disease.  Probably  not.  There  is 
much  that  militates  against  it,  especially  the  prevailing  tone  of  society.  We 
are  feeling  something  of  that  moral  laxity  which  always  follows  war.  Some 
weeks  ago  we  were  informed  that  our  dances  are  30  per  cent,  more  im- 
moral than  they  were  one  year  ago,  and  150  per  cent,  more  immoral  than 
ten  years  ago,  and  there  is  much  more  which  points  the  same  way.  Never- 
theless, we  can  not  question  that  this  campaign  has  done  good,  if  not  in 
lessening  the  actual  number  of  cases,  in  preventing  such  an  increase  as 
might  otherwise  have  taken  place. 

When  society  has  assumed  its  normal  tone,  if  the  campaign  is  conducted 
on  the  lines  I  have  just  indicated,  it  will  achieve  great  results.  But  even 
then  one  must  not  expect  too  much ;  even  then  there  would  still  be  a  la- 
mentable amount  of  venereal  disease.  To  bring  this  anywhere  near  the 
vanishing  point  something  more  radical  is  necessary.  This  something  is 
education.  It  is  true  much  has  already  been  done  by  means  of  lectures, 
already  mentioned,  and  the  results  have  been  good.  But  the  education  I 
have  in  mind  is  more  than  that.  It  is  the  education  that  can  be  given  to  all 
and  at  a  time  of  life  when  harm  has  not  yet  been  done  and  when  it  can 
influence  the  whole  life.  I  am  alluding,  of  course,  to  the  sex  education  of 
the  young.     This  means  essentially  education  in  the  home. 

All  the  testimony  we  have  points  to  the  value  of  this  teaching.  Ques- 
tionnaires here  and  there  have  brought  out  that  the  results  are  always  good. 
But  there  is  comparatively  little  such  teaching.  An  inquiry  among  thou- 
sands of  college  men  revealed  that  only  4  per  cent  of  them  had  been  taught 
at  home,  and  Dr.  Richards,  a  high  school  teacher  of  girls  in  Philadelphia, 
stated  that  only  from  i/^  to  2  per  cent,  of  her  girls  had  received  any  sex 
instruction  in  their  own  homes. 

You  know  the  usual  mode  of  sex  instruction:  The  child  gets  it  on  the 
street  and  gets  bad  and  perverted  ideas.  On  account  of  the  way  it  is  taught 
and  because  its  questions  receive  the  harsh  word  at  home,  it  is  led  to  look 
upon  these  matters  as  shameful,  and  so  is  separated  from  its  parents.  In 
a  way,  it  leads  a  secret  life.  When  the  boy  gets  older  he  is  taught  by  the 
gang  that  sexual  indulgence  is  necessary  for  health.  This  and  like  in- 
fluences lead  him  to  an  illicit  sexual  life. 

The  teaching  should  be  just  the  opposite  to  this.  It  should  be  in  the  home. 
The  parents  should  be  the  teachers;  of  the  growing  child,  the  mother.  The 
teaching  should  be  according  to  the  child's  age  and  needs,  beginning  when 
its  curiosity  is  aroused  and  it  asks  questions.     It  should  be  done  in  such  a 

Page  ilS 


RAXSOHOFF  MEMORIAL  VOLUME 


manner  as  to  arouse  a  reverent  spirit  in  the  child.  It  should  he  led  not 
to  discuss  the  matter  with  others,  hut  to  always  come  to  the  mother  when 
it  wants  information  of  this  kind  and  to  make  of  her  an  utter  confidant. 

Taught  in  this  way  instead  of  looking  upon  these  things  as  shameful,  it 
sees  the  heauty  and  sanctity  of  life.  It  acquires  knowledge  which  safe- 
guards it  from  many  pitfalls.  It  gets  high  ideals.  Above  all,  it  gets  an 
utter  confidant  in  the  mother,  often  its  means  of  salvation.  One  can  not 
rate  too  highly  the  value  to  the  child  of  this  utter  confidant.  She  is  often 
enabled  to  safeguard  it  from  impulses  in  its  own  heart  and  from  countless 
corrupting  influences  about  it.  It  is  not  so  rare  that  a  single  child  has 
corrupted  a  whole  group  of  children  or  almost  a  whole  school,  where  a 
mother,  having  the  confidence  of  her  child,  could  have  prevented  the  trouble 
or  at  least  stemmed  the  tide  of  corruption.  The  mother  should  teach  the 
young  child,  but.  when  the  boy  is  older,  the  father  should  play  his  part. 

It  is  because  so  few  parents  teach  their  children  that  there  is  demand 
for  sex  instruction  in  the  school.  This  is  part  of  the  program  of  the  na- 
tional campaign  against  the  venereal  diseases  and  really  its  most  important 
part.  But  as  yet  nothing  has  been  done  except  the  beginning  of  prepara- 
tion of  teachers.  Teachers  should  be  thoroughly  competent.  There  is 
no  doubt  that  unprepared  and  incompetent  teachers  can  do  much  harm. 

The  teaching  should  begin  with  the  young  child.  The  consensus  of 
opinion  is  that  the  child  should  be  led  gradually  from  the  knowledge  of 
reproduction  in  plant  and  animal  to  human  reproduction  and  that  the 
teaching  should  be  a  part  of  a  general  course,  such  as  physiology,  biology, 
domestic  science  or  physical  education,  so  that  this  knowledge  will  come 
to  the  child  almost  imperceptibly. 

School  instructions  might  be  of  infinite  value,  for  thrreh\  all  children 
could  get  the  right  sex  education.  Children  could  get  not  only  knowledge 
to  safeguard  them  and  ideals  to  elevate  them,  but  also  better  companions, 
companions  who  have  also  had  sex  instruction,  as  well  as  find  less  corrupt- 
ing influences  in  society,  for  with  universal  sex  instruction  the  tone  of  so- 
ciety would  be  elevated.  Not  the  least,  perhaps  the  greatest,  benefit  of 
school  instructions  would  be  that  it  would  prepare  a  new  generation  of 
parents  who  would  give  their  own  children  sex  instruction. 

Just  a  word  more.  There  are  often  violent  outbreaks  of  disease,  even 
widespread,  where  the  jjecple  can  throw  all  the  responsibility  upon  the 
health  authorities  with  the  assurance,  ])rovided  due  support  be  given  them, 
that  the  diseases  will  be  stamiicd  uul.  Xot  so  the  venereal  diseases.  Health 
authorities  alone  can  nt)t  stamp  them  out  or  come  anywhere  near  doing 
so.  The  whole  responsibility  can  not  be  thrust  upon  them.  Tiiese  are  the 
most  widespread,  the  most  menacing  ol'  all  di>ea'-(s.  They  are  a  world 
]M-oblem  and  a  jiersonal  problem.  <  »iight  not  cxeryone.  ought  not  each  of 
us,  feel  and  assume  his  >li:irc  ut'  that  rc>pun>iliility.  a  rcsi)onsibility  met 
Iiy  trying  to  understand  the  problem  and  its  solution.  !)y  his  conduct  and 
bv  his  influence? 


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